Breast Cancer

This spring, the US Food and Drug Administration approved a second cyclin-dependent kinase (CDK) inhibitor for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer in combination with aromatase inhibitors (AIs).¹ The drug, ribociclib, joins palbociclib as the second drug in this class, which targets key regulators of the mammalian cell cycle and can help to overcome resistance to endocrine therapy–like AIs, a standard front-line treatment option in this group of patients. Palbociclib (Ibrance) was approved last year in combination with the AI letrozole, which was recently expanded to include its use in combination with all AIs, the same indication for which ribociclib received approval.

The ribociclib approval was based on the results of a phase 3, randomized, double-blind, placebo-controlled, international clinical trial called MONALEESA-2.² The trial, conducted in 29 countries, compared the effects of ribociclib plus letrozole with letrozole plus placebo in 668 postmenopausal women with locally confirmed, HR-positive, HER2-negative, recurrent or metastatic breast cancer.

Patients had not received previous systemic therapy for advanced disease, had measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), had an Eastern Cooperative Oncology Group performance status of 0 or 1 (range, 1-5; 0, fully active and 5, dead), and had adequate bone marrow and organ function.

Patients were excluded if they had received previous CDK4/6 therapy, any previous systemic chemotherapy, endocrine therapy for advanced disease, previous neoadjuvant or adjuvant therapy with any nonsteroidal AI (unless they had been disease free for more than 12 months), and had inflammatory breast cancer, central nervous system metastases, history of cardiac disease or dysfunction, or impaired gastrointestinal function that alters drug absorption.

Patients were treated with ribociclib at a dose of 600 mg daily on a 3-weeks-on, 1-week-off schedule in 28-day cycles or placebo, which were combined with letrozole at a dose of 2.5 mg a day on a continuous schedule. Randomization was stratified according to the presence or absence of liver or lung metastases and treatment was continued until disease progression, unacceptable toxicity, death or discontinuation of treatment. Dose reductions of ribociclib were allowed, to manage adverse events (AEs), but treatment crossover was not permitted.

Tumor assessments were performed at screening, every 8 weeks during the first 18 months, every 12 weeks thereafter until disease progression, and at the end of treatment, and were assessed by an independent review committee. The baseline characteristics of the patient population were well balanced; patients had a median age of 62 years, all were HR positive except 1 patient who was HER2 positive.

The trial was ended prematurely after an initial interim analysis demonstrated a significant benefit in favor of ribociclib in the primary endpoint, progression-free survival (PFS). Over a median duration of follow-up of 15.3 months, the median PFS was not yet reached in the ribociclib arm, compared with 14.7 months in the placebo arm (hazard ratio, 0.556; P < .0001). In a subsequent analysis with 11 months of additional follow-up, the median PFS was 25.3 months in the combination arm, compared with 16 months in the placebo arm, which translated into a 44% reduction in the risk of disease progression or death. The PFS benefit with ribociclib was observed across all preplanned subgroup analyses. The objective response rates were 52.7% in the ribociclib arm, compared with 37.1% in the placebo arm, but overall survival data were immature.

The frequency and severity of AEs were increased in the combination arm; most common were neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain. The most common grade 3 or 4 AEs experienced with ribociclib were neutropenia, leukopenia, abnormal liver function tests, lymphopenia, and vomiting.

Ribociclib is accompanied by warnings and precautions about QT interval prolongation, hepatobiliary toxicity, and neutropenia. Clinicians are advised to monitor electrocardiograms and electrolytes before the start of ribociclib therapy and to begin treatment only in patients with QTcF values <450 ms and in whom electrolyte abnormalities have been corrected. ECG should be repeated at around day 14 of the first cycle, the beginning of the second cycle, and as deemed clinically necessary.

Liver function tests should be performed before starting treatment, every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, and as clinically indicated. For aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels greater than 3-5 times the upper limit of normal (ULN, grade 2), ribociclib should be interrupted until recovery to baseline or lower. For levels >5-20 times the ULN (grade 3) or recurring grade 2 increases, treatment should be interrupted until recovery to baseline or lower and then resumed at the next lowest dose level. Treatment with ribociclib should be discontinued in the event of recurring grade 3 elevations or for AST/ALT elevations >3 times ULN in combination with total bilirubin >2 times ULN.

Complete blood counts should be performed before starting treatment and monitored every 2 weeks for the first 2 cycles, at the beginning of each of the 4 subsequent cycles, and as clinically needed. If absolute neutrophil counts are 500-1,000 mm³ (grade 3), treatment should be discontinued until recovery to grade 2 or lower. If grade 3 neutropenia recurs or for grade 3 febrile neutropenia or grade 4 neutropenia, treatment should resume at a lower dose level upon recovery to grade 2 or lower.

Pregnant women and those of reproductive age should be warned of the risk of fetal harm and the need for effective contraception during treatment and for at least 3 weeks after the last dose. Ribociclib is marketed as Kisqali by Novartis.

This spring, the US Food and Drug Administration approved a second cyclin-dependent kinase (CDK) inhibitor for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer in combination with aromatase inhibitors (AIs).¹ The drug, ribociclib, joins palbociclib as the second drug in this class, which targets key regulators of the mammalian cell cycle and can help to overcome resistance to endocrine therapy–like AIs, a standard front-line treatment option in this group of patients. Palbociclib (Ibrance) was approved last year in combination with the AI letrozole, which was recently expanded to include its use in combination with all AIs, the same indication for which ribociclib received approval.

The ribociclib approval was based on the results of a phase 3, randomized, double-blind, placebo-controlled, international clinical trial called MONALEESA-2.² The trial, conducted in 29 countries, compared the effects of ribociclib plus letrozole with letrozole plus placebo in 668 postmenopausal women with locally confirmed, HR-positive, HER2-negative, recurrent or metastatic breast cancer.

Patients had not received previous systemic therapy for advanced disease, had measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), had an Eastern Cooperative Oncology Group performance status of 0 or 1 (range, 1-5; 0, fully active and 5, dead), and had adequate bone marrow and organ function.

Patients were excluded if they had received previous CDK4/6 therapy, any previous systemic chemotherapy, endocrine therapy for advanced disease, previous neoadjuvant or adjuvant therapy with any nonsteroidal AI (unless they had been disease free for more than 12 months), and had inflammatory breast cancer, central nervous system metastases, history of cardiac disease or dysfunction, or impaired gastrointestinal function that alters drug absorption.

Patients were treated with ribociclib at a dose of 600 mg daily on a 3-weeks-on, 1-week-off schedule in 28-day cycles or placebo, which were combined with letrozole at a dose of 2.5 mg a day on a continuous schedule. Randomization was stratified according to the presence or absence of liver or lung metastases and treatment was continued until disease progression, unacceptable toxicity, death or discontinuation of treatment. Dose reductions of ribociclib were allowed, to manage adverse events (AEs), but treatment crossover was not permitted.

Tumor assessments were performed at screening, every 8 weeks during the first 18 months, every 12 weeks thereafter until disease progression, and at the end of treatment, and were assessed by an independent review committee. The baseline characteristics of the patient population were well balanced; patients had a median age of 62 years, all were HR positive except 1 patient who was HER2 positive.

The trial was ended prematurely after an initial interim analysis demonstrated a significant benefit in favor of ribociclib in the primary endpoint, progression-free survival (PFS). Over a median duration of follow-up of 15.3 months, the median PFS was not yet reached in the ribociclib arm, compared with 14.7 months in the placebo arm (hazard ratio, 0.556; P < .0001). In a subsequent analysis with 11 months of additional follow-up, the median PFS was 25.3 months in the combination arm, compared with 16 months in the placebo arm, which translated into a 44% reduction in the risk of disease progression or death. The PFS benefit with ribociclib was observed across all preplanned subgroup analyses. The objective response rates were 52.7% in the ribociclib arm, compared with 37.1% in the placebo arm, but overall survival data were immature.

The frequency and severity of AEs were increased in the combination arm; most common were neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain. The most common grade 3 or 4 AEs experienced with ribociclib were neutropenia, leukopenia, abnormal liver function tests, lymphopenia, and vomiting.

Ribociclib is accompanied by warnings and precautions about QT interval prolongation, hepatobiliary toxicity, and neutropenia. Clinicians are advised to monitor electrocardiograms and electrolytes before the start of ribociclib therapy and to begin treatment only in patients with QTcF values <450 ms and in whom electrolyte abnormalities have been corrected. ECG should be repeated at around day 14 of the first cycle, the beginning of the second cycle, and as deemed clinically necessary.

Liver function tests should be performed before starting treatment, every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, and as clinically indicated. For aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels greater than 3-5 times the upper limit of normal (ULN, grade 2), ribociclib should be interrupted until recovery to baseline or lower. For levels >5-20 times the ULN (grade 3) or recurring grade 2 increases, treatment should be interrupted until recovery to baseline or lower and then resumed at the next lowest dose level. Treatment with ribociclib should be discontinued in the event of recurring grade 3 elevations or for AST/ALT elevations >3 times ULN in combination with total bilirubin >2 times ULN.

Complete blood counts should be performed before starting treatment and monitored every 2 weeks for the first 2 cycles, at the beginning of each of the 4 subsequent cycles, and as clinically needed. If absolute neutrophil counts are 500-1,000 mm³ (grade 3), treatment should be discontinued until recovery to grade 2 or lower. If grade 3 neutropenia recurs or for grade 3 febrile neutropenia or grade 4 neutropenia, treatment should resume at a lower dose level upon recovery to grade 2 or lower.

Pregnant women and those of reproductive age should be warned of the risk of fetal harm and the need for effective contraception during treatment and for at least 3 weeks after the last dose. Ribociclib is marketed as Kisqali by Novartis.

This spring, the US Food and Drug Administration approved a second cyclin-dependent kinase (CDK) inhibitor for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer in combination with aromatase inhibitors (AIs).¹ The drug, ribociclib, joins palbociclib as the second drug in this class, which targets key regulators of the mammalian cell cycle and can help to overcome resistance to endocrine therapy–like AIs, a standard front-line treatment option in this group of patients. Palbociclib (Ibrance) was approved last year in combination with the AI letrozole, which was recently expanded to include its use in combination with all AIs, the same indication for which ribociclib received approval.

The ribociclib approval was based on the results of a phase 3, randomized, double-blind, placebo-controlled, international clinical trial called MONALEESA-2.² The trial, conducted in 29 countries, compared the effects of ribociclib plus letrozole with letrozole plus placebo in 668 postmenopausal women with locally confirmed, HR-positive, HER2-negative, recurrent or metastatic breast cancer.

Patients had not received previous systemic therapy for advanced disease, had measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), had an Eastern Cooperative Oncology Group performance status of 0 or 1 (range, 1-5; 0, fully active and 5, dead), and had adequate bone marrow and organ function.

Patients were excluded if they had received previous CDK4/6 therapy, any previous systemic chemotherapy, endocrine therapy for advanced disease, previous neoadjuvant or adjuvant therapy with any nonsteroidal AI (unless they had been disease free for more than 12 months), and had inflammatory breast cancer, central nervous system metastases, history of cardiac disease or dysfunction, or impaired gastrointestinal function that alters drug absorption.

Patients were treated with ribociclib at a dose of 600 mg daily on a 3-weeks-on, 1-week-off schedule in 28-day cycles or placebo, which were combined with letrozole at a dose of 2.5 mg a day on a continuous schedule. Randomization was stratified according to the presence or absence of liver or lung metastases and treatment was continued until disease progression, unacceptable toxicity, death or discontinuation of treatment. Dose reductions of ribociclib were allowed, to manage adverse events (AEs), but treatment crossover was not permitted.

Tumor assessments were performed at screening, every 8 weeks during the first 18 months, every 12 weeks thereafter until disease progression, and at the end of treatment, and were assessed by an independent review committee. The baseline characteristics of the patient population were well balanced; patients had a median age of 62 years, all were HR positive except 1 patient who was HER2 positive.

The trial was ended prematurely after an initial interim analysis demonstrated a significant benefit in favor of ribociclib in the primary endpoint, progression-free survival (PFS). Over a median duration of follow-up of 15.3 months, the median PFS was not yet reached in the ribociclib arm, compared with 14.7 months in the placebo arm (hazard ratio, 0.556; P < .0001). In a subsequent analysis with 11 months of additional follow-up, the median PFS was 25.3 months in the combination arm, compared with 16 months in the placebo arm, which translated into a 44% reduction in the risk of disease progression or death. The PFS benefit with ribociclib was observed across all preplanned subgroup analyses. The objective response rates were 52.7% in the ribociclib arm, compared with 37.1% in the placebo arm, but overall survival data were immature.

The frequency and severity of AEs were increased in the combination arm; most common were neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain. The most common grade 3 or 4 AEs experienced with ribociclib were neutropenia, leukopenia, abnormal liver function tests, lymphopenia, and vomiting.

Ribociclib is accompanied by warnings and precautions about QT interval prolongation, hepatobiliary toxicity, and neutropenia. Clinicians are advised to monitor electrocardiograms and electrolytes before the start of ribociclib therapy and to begin treatment only in patients with QTcF values <450 ms and in whom electrolyte abnormalities have been corrected. ECG should be repeated at around day 14 of the first cycle, the beginning of the second cycle, and as deemed clinically necessary.

Liver function tests should be performed before starting treatment, every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, and as clinically indicated. For aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels greater than 3-5 times the upper limit of normal (ULN, grade 2), ribociclib should be interrupted until recovery to baseline or lower. For levels >5-20 times the ULN (grade 3) or recurring grade 2 increases, treatment should be interrupted until recovery to baseline or lower and then resumed at the next lowest dose level. Treatment with ribociclib should be discontinued in the event of recurring grade 3 elevations or for AST/ALT elevations >3 times ULN in combination with total bilirubin >2 times ULN.

Complete blood counts should be performed before starting treatment and monitored every 2 weeks for the first 2 cycles, at the beginning of each of the 4 subsequent cycles, and as clinically needed. If absolute neutrophil counts are 500-1,000 mm³ (grade 3), treatment should be discontinued until recovery to grade 2 or lower. If grade 3 neutropenia recurs or for grade 3 febrile neutropenia or grade 4 neutropenia, treatment should resume at a lower dose level upon recovery to grade 2 or lower.

Pregnant women and those of reproductive age should be warned of the risk of fetal harm and the need for effective contraception during treatment and for at least 3 weeks after the last dose. Ribociclib is marketed as Kisqali by Novartis.

Broader cancer screening of individuals with Li-Fraumeni syndrome (LFS), with or without whole-body magnetic resonance imaging, has a good diagnostic yield and identifies a wide range of cancers, according to a preliminary analysis of the ongoing LIFSCREEN phase 3, randomized, controlled trial.

Investigators led by Olivier Caron, MD, chair of the oncogenetics committee, department of medical oncology, at the Gustave Roussy University Hospital in Villejuif, France, enrolled in the trial 107 individuals from 75 families carrying a TP53 mutation, a genetic aberration commonly present in LFS that confers heightened risk of a variety of malignancies.

Participants had a median age at baseline of 32.9 years, with a range from 5 to 67 years. Fully 98% had a family history of cancer, and 48% had a personal history of cancer.

The participants were assigned to 5 years of standard screening – annual clinical examination, abdomen and pelvis ultrasound, brain MRI, complete blood cell count, and, for women older than 20 years, breast ultrasound and MRI – or intensive screening, entailing the addition of diffusion whole-body MRI.

At the time of the preliminary analysis, 15 patients had undergone only one round of screening; 35, two rounds; 19, three rounds; 24, four rounds; and 7, five rounds, Dr. Caron and associates reported in a research letter (JAMA Oncol. 2017; Aug 3 doi: 10.1001/jamaoncol.2017.1358).

Collectively, this amounted to 226.4 person-years of follow-up.

Screening with either trial strategy (with or without whole-body MRI) led to diagnosis of 23 new primary cancers in 20 patients. Nearly half of the total (12 cancers) were detected at the first round. Patients had a median age of 39.8 at the new cancer diagnosis, with a range from 6 to 70 years.

Of the new cancers, 10 belonged to the core LFS spectrum of breast cancer, sarcoma, and brain tumors. However, the other 13 were outside that spectrum, for example, lung adenocarcinomas, all seen in never or light smokers, and leukemias. Screening also detected three relapses of previous cancers.

Analyses further showed that prior cancer diagnosis was not a reliable marker for risk of new primaries. Although 12 of the patients with a screening-detected new primary had a personal cancer history, 8 did not (P = .22).

“The proportion and diversity of off–core LFS spectrum cancers detected in TP53 mutation carriers as reported by others give growing evidence of a broader LFS spectrum, in agreement with the permissive role of TP53 mutations,” write Dr. Caron and colleagues, who report having no relevant disclosures. “Our observations seem to support recent moves toward broader cancer screening in TP53 mutation carriers.”

The investigators continue to collect data in LIFSCREEN and plan to undertake main analysis later this year. “Our final analysis will help to determine the benefits and drawbacks (mostly related to false-positive test results) of whole-body MRI in TP53 mutation carrier surveillance,” they conclude. “Studies focused on TP53 mutation penetrance, using methods limiting selection bias, are required to refine cancer risks to improve TP53 mutation carrier management.”

Broader cancer screening of individuals with Li-Fraumeni syndrome (LFS), with or without whole-body magnetic resonance imaging, has a good diagnostic yield and identifies a wide range of cancers, according to a preliminary analysis of the ongoing LIFSCREEN phase 3, randomized, controlled trial.

Investigators led by Olivier Caron, MD, chair of the oncogenetics committee, department of medical oncology, at the Gustave Roussy University Hospital in Villejuif, France, enrolled in the trial 107 individuals from 75 families carrying a TP53 mutation, a genetic aberration commonly present in LFS that confers heightened risk of a variety of malignancies.

Participants had a median age at baseline of 32.9 years, with a range from 5 to 67 years. Fully 98% had a family history of cancer, and 48% had a personal history of cancer.

The participants were assigned to 5 years of standard screening – annual clinical examination, abdomen and pelvis ultrasound, brain MRI, complete blood cell count, and, for women older than 20 years, breast ultrasound and MRI – or intensive screening, entailing the addition of diffusion whole-body MRI.

At the time of the preliminary analysis, 15 patients had undergone only one round of screening; 35, two rounds; 19, three rounds; 24, four rounds; and 7, five rounds, Dr. Caron and associates reported in a research letter (JAMA Oncol. 2017; Aug 3 doi: 10.1001/jamaoncol.2017.1358).

Collectively, this amounted to 226.4 person-years of follow-up.

Screening with either trial strategy (with or without whole-body MRI) led to diagnosis of 23 new primary cancers in 20 patients. Nearly half of the total (12 cancers) were detected at the first round. Patients had a median age of 39.8 at the new cancer diagnosis, with a range from 6 to 70 years.

Of the new cancers, 10 belonged to the core LFS spectrum of breast cancer, sarcoma, and brain tumors. However, the other 13 were outside that spectrum, for example, lung adenocarcinomas, all seen in never or light smokers, and leukemias. Screening also detected three relapses of previous cancers.

Analyses further showed that prior cancer diagnosis was not a reliable marker for risk of new primaries. Although 12 of the patients with a screening-detected new primary had a personal cancer history, 8 did not (P = .22).

“The proportion and diversity of off–core LFS spectrum cancers detected in TP53 mutation carriers as reported by others give growing evidence of a broader LFS spectrum, in agreement with the permissive role of TP53 mutations,” write Dr. Caron and colleagues, who report having no relevant disclosures. “Our observations seem to support recent moves toward broader cancer screening in TP53 mutation carriers.”

The investigators continue to collect data in LIFSCREEN and plan to undertake main analysis later this year. “Our final analysis will help to determine the benefits and drawbacks (mostly related to false-positive test results) of whole-body MRI in TP53 mutation carrier surveillance,” they conclude. “Studies focused on TP53 mutation penetrance, using methods limiting selection bias, are required to refine cancer risks to improve TP53 mutation carrier management.”

Broader cancer screening of individuals with Li-Fraumeni syndrome (LFS), with or without whole-body magnetic resonance imaging, has a good diagnostic yield and identifies a wide range of cancers, according to a preliminary analysis of the ongoing LIFSCREEN phase 3, randomized, controlled trial.

Investigators led by Olivier Caron, MD, chair of the oncogenetics committee, department of medical oncology, at the Gustave Roussy University Hospital in Villejuif, France, enrolled in the trial 107 individuals from 75 families carrying a TP53 mutation, a genetic aberration commonly present in LFS that confers heightened risk of a variety of malignancies.

Participants had a median age at baseline of 32.9 years, with a range from 5 to 67 years. Fully 98% had a family history of cancer, and 48% had a personal history of cancer.

The participants were assigned to 5 years of standard screening – annual clinical examination, abdomen and pelvis ultrasound, brain MRI, complete blood cell count, and, for women older than 20 years, breast ultrasound and MRI – or intensive screening, entailing the addition of diffusion whole-body MRI.

At the time of the preliminary analysis, 15 patients had undergone only one round of screening; 35, two rounds; 19, three rounds; 24, four rounds; and 7, five rounds, Dr. Caron and associates reported in a research letter (JAMA Oncol. 2017; Aug 3 doi: 10.1001/jamaoncol.2017.1358).

Collectively, this amounted to 226.4 person-years of follow-up.

Screening with either trial strategy (with or without whole-body MRI) led to diagnosis of 23 new primary cancers in 20 patients. Nearly half of the total (12 cancers) were detected at the first round. Patients had a median age of 39.8 at the new cancer diagnosis, with a range from 6 to 70 years.

Of the new cancers, 10 belonged to the core LFS spectrum of breast cancer, sarcoma, and brain tumors. However, the other 13 were outside that spectrum, for example, lung adenocarcinomas, all seen in never or light smokers, and leukemias. Screening also detected three relapses of previous cancers.

Analyses further showed that prior cancer diagnosis was not a reliable marker for risk of new primaries. Although 12 of the patients with a screening-detected new primary had a personal cancer history, 8 did not (P = .22).

“The proportion and diversity of off–core LFS spectrum cancers detected in TP53 mutation carriers as reported by others give growing evidence of a broader LFS spectrum, in agreement with the permissive role of TP53 mutations,” write Dr. Caron and colleagues, who report having no relevant disclosures. “Our observations seem to support recent moves toward broader cancer screening in TP53 mutation carriers.”

The investigators continue to collect data in LIFSCREEN and plan to undertake main analysis later this year. “Our final analysis will help to determine the benefits and drawbacks (mostly related to false-positive test results) of whole-body MRI in TP53 mutation carrier surveillance,” they conclude. “Studies focused on TP53 mutation penetrance, using methods limiting selection bias, are required to refine cancer risks to improve TP53 mutation carrier management.”

More women are living longer with distant metastatic breast cancer (MBC), according to a National Cancer Institute study. Between 1992-1994 and 2005-2012, 5-year relative survival among women who were diagnosed with MBC at ages 15 to 49 doubled, from 18% to 36%.

Researchers also found that relative survival time increased from 22.3 months to 38.7 months for women diagnosed aged 15 -49 years, and from 19.1 months to 29.7 months for those aged 50 – 64 years.

Moreover, a “small but meaningful” number of women are living years after an initial diagnosis of MBC, the study found. More than 11% of women diagnosed between 2000-2004 aged < 64 years survived ≥ 10 years. Although nearly half of women with MBC have had it for ≤ 2 , one third have lived with it for ≥ 5 years.

The study findings “make clear that the majority of MBC patients, those who are diagnosed with non-metastatic cancer but progress to distant disease, have never been properly documented,” said Angela Mariotto, PhD, chief of the NCI Data Analytics Branch of the Division of Cancer Control and Population Sciences. By including women with recurrence, the study provides a more accurate number of women in the U.S. living with MBC, which can help with health care planning.

More women are living longer with distant metastatic breast cancer (MBC), according to a National Cancer Institute study. Between 1992-1994 and 2005-2012, 5-year relative survival among women who were diagnosed with MBC at ages 15 to 49 doubled, from 18% to 36%.

Researchers also found that relative survival time increased from 22.3 months to 38.7 months for women diagnosed aged 15 -49 years, and from 19.1 months to 29.7 months for those aged 50 – 64 years.

Moreover, a “small but meaningful” number of women are living years after an initial diagnosis of MBC, the study found. More than 11% of women diagnosed between 2000-2004 aged < 64 years survived ≥ 10 years. Although nearly half of women with MBC have had it for ≤ 2 , one third have lived with it for ≥ 5 years.

The study findings “make clear that the majority of MBC patients, those who are diagnosed with non-metastatic cancer but progress to distant disease, have never been properly documented,” said Angela Mariotto, PhD, chief of the NCI Data Analytics Branch of the Division of Cancer Control and Population Sciences. By including women with recurrence, the study provides a more accurate number of women in the U.S. living with MBC, which can help with health care planning.

More women are living longer with distant metastatic breast cancer (MBC), according to a National Cancer Institute study. Between 1992-1994 and 2005-2012, 5-year relative survival among women who were diagnosed with MBC at ages 15 to 49 doubled, from 18% to 36%.

Researchers also found that relative survival time increased from 22.3 months to 38.7 months for women diagnosed aged 15 -49 years, and from 19.1 months to 29.7 months for those aged 50 – 64 years.

Moreover, a “small but meaningful” number of women are living years after an initial diagnosis of MBC, the study found. More than 11% of women diagnosed between 2000-2004 aged < 64 years survived ≥ 10 years. Although nearly half of women with MBC have had it for ≤ 2 , one third have lived with it for ≥ 5 years.

The study findings “make clear that the majority of MBC patients, those who are diagnosed with non-metastatic cancer but progress to distant disease, have never been properly documented,” said Angela Mariotto, PhD, chief of the NCI Data Analytics Branch of the Division of Cancer Control and Population Sciences. By including women with recurrence, the study provides a more accurate number of women in the U.S. living with MBC, which can help with health care planning.

The Food and Drug Administration has approved neratinib, an oral tyrosine kinase inhibitor, for the extended adjuvant treatment of patients with early-stage, HER2-positive breast cancer who have previously been treated with trastuzumab.

Approval was based on improved invasive disease-free survival (iDFS) in the phase 3 ExteNET trial of 2,840 women with early-stage HER2-positive breast cancer who were within 2 years of completing adjuvant trastuzumab. Patients were randomized to receive either neratinib or placebo daily for 1 year. After 2 years of follow-up, iDFS was 94.2% in patients treated with neratinib, compared with 91.9% in those receiving placebo (hazard ratio, 0.66; 95% confidence interval, 0.49, 0.90; P = .008), according to the FDA statement.

[email protected]

The Food and Drug Administration has approved neratinib, an oral tyrosine kinase inhibitor, for the extended adjuvant treatment of patients with early-stage, HER2-positive breast cancer who have previously been treated with trastuzumab.

Approval was based on improved invasive disease-free survival (iDFS) in the phase 3 ExteNET trial of 2,840 women with early-stage HER2-positive breast cancer who were within 2 years of completing adjuvant trastuzumab. Patients were randomized to receive either neratinib or placebo daily for 1 year. After 2 years of follow-up, iDFS was 94.2% in patients treated with neratinib, compared with 91.9% in those receiving placebo (hazard ratio, 0.66; 95% confidence interval, 0.49, 0.90; P = .008), according to the FDA statement.

[email protected]

The Food and Drug Administration has approved neratinib, an oral tyrosine kinase inhibitor, for the extended adjuvant treatment of patients with early-stage, HER2-positive breast cancer who have previously been treated with trastuzumab.

Approval was based on improved invasive disease-free survival (iDFS) in the phase 3 ExteNET trial of 2,840 women with early-stage HER2-positive breast cancer who were within 2 years of completing adjuvant trastuzumab. Patients were randomized to receive either neratinib or placebo daily for 1 year. After 2 years of follow-up, iDFS was 94.2% in patients treated with neratinib, compared with 91.9% in those receiving placebo (hazard ratio, 0.66; 95% confidence interval, 0.49, 0.90; P = .008), according to the FDA statement.

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Use of Pap smears and mammography has slowly but steadily declined since both peaked in the year 2000, according to the National Center for Health Statistics.

The age-adjusted rate of women aged 18 years and over who reported having had a Pap smear in the past 3 years dropped from 81.3% in 2000 to 70.2% in 2015. Over that same time period, the age-adjusted rate of women aged 40 years and over who had a mammogram over the previous 2 years declined from 70.4% in 2000 to 64% in 2015, the NCHS reported in “Health, United States, 2016.”

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Use of Pap smears and mammography has slowly but steadily declined since both peaked in the year 2000, according to the National Center for Health Statistics.

The age-adjusted rate of women aged 18 years and over who reported having had a Pap smear in the past 3 years dropped from 81.3% in 2000 to 70.2% in 2015. Over that same time period, the age-adjusted rate of women aged 40 years and over who had a mammogram over the previous 2 years declined from 70.4% in 2000 to 64% in 2015, the NCHS reported in “Health, United States, 2016.”

[email protected]

Use of Pap smears and mammography has slowly but steadily declined since both peaked in the year 2000, according to the National Center for Health Statistics.

The age-adjusted rate of women aged 18 years and over who reported having had a Pap smear in the past 3 years dropped from 81.3% in 2000 to 70.2% in 2015. Over that same time period, the age-adjusted rate of women aged 40 years and over who had a mammogram over the previous 2 years declined from 70.4% in 2000 to 64% in 2015, the NCHS reported in “Health, United States, 2016.”

[email protected]

LAS VEGAS – Radiation oncologists at the University of Texas MD Anderson Cancer Center, Houston, were able to complete 98% of their radiotherapy plans when women received temporary tissue expanders, instead of immediate reconstructions, at the time of skin-sparing mastectomy, in a series of 384 women, most with stage 2-3 breast cancer.

The expanders – saline-filled bags commonly used in plastic surgery to create new skin – were kept in place but deflated for radiotherapy, which allowed for optimal access to treatment fields; the final reconstruction, successful in 90% of women, came a median of 7 months following radiation.

M. Alexander Otto/Frontline Medical News

[email protected]

LAS VEGAS – Radiation oncologists at the University of Texas MD Anderson Cancer Center, Houston, were able to complete 98% of their radiotherapy plans when women received temporary tissue expanders, instead of immediate reconstructions, at the time of skin-sparing mastectomy, in a series of 384 women, most with stage 2-3 breast cancer.

The expanders – saline-filled bags commonly used in plastic surgery to create new skin – were kept in place but deflated for radiotherapy, which allowed for optimal access to treatment fields; the final reconstruction, successful in 90% of women, came a median of 7 months following radiation.

M. Alexander Otto/Frontline Medical News

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LAS VEGAS – Radiation oncologists at the University of Texas MD Anderson Cancer Center, Houston, were able to complete 98% of their radiotherapy plans when women received temporary tissue expanders, instead of immediate reconstructions, at the time of skin-sparing mastectomy, in a series of 384 women, most with stage 2-3 breast cancer.

The expanders – saline-filled bags commonly used in plastic surgery to create new skin – were kept in place but deflated for radiotherapy, which allowed for optimal access to treatment fields; the final reconstruction, successful in 90% of women, came a median of 7 months following radiation.

M. Alexander Otto/Frontline Medical News

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A spike in later-stage breast cancers is a potential byproduct of the Republican-proposed Medicaid reductions, according to Wafa Tarazi, PhD, and her colleagues.

The team looked at breast cancer stage at diagnosis following the 2005 Medicaid disenrollment of nearly 170,000 nonelderly adults in Tennessee that occurred because of state financial issues.

“Overall, nonelderly women in Tennessee were diagnosed at later stages of disease and experienced more delays in treatment in the period after disenrollment,” wrote Dr. Tarazi of Virginia Commonwealth University, Richmond, and her colleagues. “Disenrollment was found to be associated with a 3.3 percentage point increase in late stage of disease at the time of diagnosis” (Cancer 2016 June 26. doi: 10.1002/cncr.30771).

The investigators offered a few explanations for why this could be the case.

sndr/istockphoto.com

[email protected]

A spike in later-stage breast cancers is a potential byproduct of the Republican-proposed Medicaid reductions, according to Wafa Tarazi, PhD, and her colleagues.

The team looked at breast cancer stage at diagnosis following the 2005 Medicaid disenrollment of nearly 170,000 nonelderly adults in Tennessee that occurred because of state financial issues.

“Overall, nonelderly women in Tennessee were diagnosed at later stages of disease and experienced more delays in treatment in the period after disenrollment,” wrote Dr. Tarazi of Virginia Commonwealth University, Richmond, and her colleagues. “Disenrollment was found to be associated with a 3.3 percentage point increase in late stage of disease at the time of diagnosis” (Cancer 2016 June 26. doi: 10.1002/cncr.30771).

The investigators offered a few explanations for why this could be the case.

sndr/istockphoto.com

[email protected]

A spike in later-stage breast cancers is a potential byproduct of the Republican-proposed Medicaid reductions, according to Wafa Tarazi, PhD, and her colleagues.

The team looked at breast cancer stage at diagnosis following the 2005 Medicaid disenrollment of nearly 170,000 nonelderly adults in Tennessee that occurred because of state financial issues.

“Overall, nonelderly women in Tennessee were diagnosed at later stages of disease and experienced more delays in treatment in the period after disenrollment,” wrote Dr. Tarazi of Virginia Commonwealth University, Richmond, and her colleagues. “Disenrollment was found to be associated with a 3.3 percentage point increase in late stage of disease at the time of diagnosis” (Cancer 2016 June 26. doi: 10.1002/cncr.30771).

The investigators offered a few explanations for why this could be the case.

sndr/istockphoto.com

[email protected]

Young women treated for early hormone receptor–positive, HER2-negative breast cancer fare better if their adjuvant endocrine therapy includes ovarian function suppression (OFS), according to a new analysis published online.

Senior author Gini F. Fleming, MD, director of the medical oncology breast program at the University of Chicago Medical Center, and her colleagues analyzed data from a pair of international phase III randomized adjuvant trials: the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT).

Main analyses were based on a respective 240 and 145 women younger than 35 years who had undergone surgery for early hormone receptor–positive, HER2-negative early breast cancer, received chemotherapy, and were randomly assigned to 5 years of various adjuvant endocrine therapies.

In SOFT, the 5-year breast cancer–free interval was 67.1% (95% CI, 54.6%-76.9%) with tamoxifen (Nolvadex) alone, 75.9% (64.0%-84.4%) with tamoxifen plus OFS, and 83.2% (72.7%-90.0%) with exemestane (Aromasin) plus OFS (J Clin Oncol. 2017 June 27 doi: 10.1200/JCO.2016.72.0946). In TEXT, it was 79.2% (66.2%-87.7%) with tamoxifen plus OFS and 81.6% (69.8%-89.2%) with exemestane plus OFS.

In a quality of life analysis among women receiving OFS, vasomotor symptoms (hot flushes and sweats) showed greatest increase from baseline (roughly 30-40 points) in the first 6 months of therapy. Loss of sexual interest and difficulties in becoming aroused were also noteworthy (8 points or greater). However, scores for global quality of life (physical well-being, mood, coping effort, and health perception) showed little change from baseline and were essentially the same as those seen among premenopausal women aged 35 or older in the same trials.

Overall, 19.8% of the young women in SOFT and TEXT stopped all protocol-assigned endocrine therapy early. The proportion rose with time and was higher than that among the older premenopausal group.

“There was a meaningful clinical benefit in breast cancer outcomes with the addition of OFS to tamoxifen and some additional benefit from use of an aromatase inhibitor with OFS. Longer follow-up is critical to clarify potential survival benefits,” the investigators wrote. “There were substantial adverse effects from these combined endocrine treatments, but they were not different in the younger and older than 35 years populations. Despite this, rates of nonadherence were slightly higher in women younger than 35 years.

“Availability of these age-specific data regarding risks and benefits of combined endocrine therapy will support shared decision making regarding OFS among young women at high risk for recurrence and death from breast cancer and, it is hoped, improve adherence among those who select OFS,” they concluded.

Young women treated for early hormone receptor–positive, HER2-negative breast cancer fare better if their adjuvant endocrine therapy includes ovarian function suppression (OFS), according to a new analysis published online.

Senior author Gini F. Fleming, MD, director of the medical oncology breast program at the University of Chicago Medical Center, and her colleagues analyzed data from a pair of international phase III randomized adjuvant trials: the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT).

Main analyses were based on a respective 240 and 145 women younger than 35 years who had undergone surgery for early hormone receptor–positive, HER2-negative early breast cancer, received chemotherapy, and were randomly assigned to 5 years of various adjuvant endocrine therapies.

In SOFT, the 5-year breast cancer–free interval was 67.1% (95% CI, 54.6%-76.9%) with tamoxifen (Nolvadex) alone, 75.9% (64.0%-84.4%) with tamoxifen plus OFS, and 83.2% (72.7%-90.0%) with exemestane (Aromasin) plus OFS (J Clin Oncol. 2017 June 27 doi: 10.1200/JCO.2016.72.0946). In TEXT, it was 79.2% (66.2%-87.7%) with tamoxifen plus OFS and 81.6% (69.8%-89.2%) with exemestane plus OFS.

In a quality of life analysis among women receiving OFS, vasomotor symptoms (hot flushes and sweats) showed greatest increase from baseline (roughly 30-40 points) in the first 6 months of therapy. Loss of sexual interest and difficulties in becoming aroused were also noteworthy (8 points or greater). However, scores for global quality of life (physical well-being, mood, coping effort, and health perception) showed little change from baseline and were essentially the same as those seen among premenopausal women aged 35 or older in the same trials.

Overall, 19.8% of the young women in SOFT and TEXT stopped all protocol-assigned endocrine therapy early. The proportion rose with time and was higher than that among the older premenopausal group.

“There was a meaningful clinical benefit in breast cancer outcomes with the addition of OFS to tamoxifen and some additional benefit from use of an aromatase inhibitor with OFS. Longer follow-up is critical to clarify potential survival benefits,” the investigators wrote. “There were substantial adverse effects from these combined endocrine treatments, but they were not different in the younger and older than 35 years populations. Despite this, rates of nonadherence were slightly higher in women younger than 35 years.

“Availability of these age-specific data regarding risks and benefits of combined endocrine therapy will support shared decision making regarding OFS among young women at high risk for recurrence and death from breast cancer and, it is hoped, improve adherence among those who select OFS,” they concluded.

Young women treated for early hormone receptor–positive, HER2-negative breast cancer fare better if their adjuvant endocrine therapy includes ovarian function suppression (OFS), according to a new analysis published online.

Senior author Gini F. Fleming, MD, director of the medical oncology breast program at the University of Chicago Medical Center, and her colleagues analyzed data from a pair of international phase III randomized adjuvant trials: the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT).

Main analyses were based on a respective 240 and 145 women younger than 35 years who had undergone surgery for early hormone receptor–positive, HER2-negative early breast cancer, received chemotherapy, and were randomly assigned to 5 years of various adjuvant endocrine therapies.

In SOFT, the 5-year breast cancer–free interval was 67.1% (95% CI, 54.6%-76.9%) with tamoxifen (Nolvadex) alone, 75.9% (64.0%-84.4%) with tamoxifen plus OFS, and 83.2% (72.7%-90.0%) with exemestane (Aromasin) plus OFS (J Clin Oncol. 2017 June 27 doi: 10.1200/JCO.2016.72.0946). In TEXT, it was 79.2% (66.2%-87.7%) with tamoxifen plus OFS and 81.6% (69.8%-89.2%) with exemestane plus OFS.

In a quality of life analysis among women receiving OFS, vasomotor symptoms (hot flushes and sweats) showed greatest increase from baseline (roughly 30-40 points) in the first 6 months of therapy. Loss of sexual interest and difficulties in becoming aroused were also noteworthy (8 points or greater). However, scores for global quality of life (physical well-being, mood, coping effort, and health perception) showed little change from baseline and were essentially the same as those seen among premenopausal women aged 35 or older in the same trials.

Overall, 19.8% of the young women in SOFT and TEXT stopped all protocol-assigned endocrine therapy early. The proportion rose with time and was higher than that among the older premenopausal group.

“There was a meaningful clinical benefit in breast cancer outcomes with the addition of OFS to tamoxifen and some additional benefit from use of an aromatase inhibitor with OFS. Longer follow-up is critical to clarify potential survival benefits,” the investigators wrote. “There were substantial adverse effects from these combined endocrine treatments, but they were not different in the younger and older than 35 years populations. Despite this, rates of nonadherence were slightly higher in women younger than 35 years.

“Availability of these age-specific data regarding risks and benefits of combined endocrine therapy will support shared decision making regarding OFS among young women at high risk for recurrence and death from breast cancer and, it is hoped, improve adherence among those who select OFS,” they concluded.

Women can reduce their risk of dying should they receive a breast cancer diagnosis by following a low-fat diet, suggests an analysis from the phase III multicenter randomized Women’s Health Initiative Dietary Modification trial.

Investigators led by Rowan T. Chlebowski, MD, PhD, formerly of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, and now at City of Hope National Medical Center, Duarte, California, analyzed data from 48,835 postmenopausal women who had never had breast cancer and had normal mammograms. The women were randomly assigned 2:3 to a diet aimed at reducing fat intake to 20% of energy and increasing intake of fruits, vegetables, and grains or to a usual diet.

Women can reduce their risk of dying should they receive a breast cancer diagnosis by following a low-fat diet, suggests an analysis from the phase III multicenter randomized Women’s Health Initiative Dietary Modification trial.

Investigators led by Rowan T. Chlebowski, MD, PhD, formerly of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, and now at City of Hope National Medical Center, Duarte, California, analyzed data from 48,835 postmenopausal women who had never had breast cancer and had normal mammograms. The women were randomly assigned 2:3 to a diet aimed at reducing fat intake to 20% of energy and increasing intake of fruits, vegetables, and grains or to a usual diet.

Women can reduce their risk of dying should they receive a breast cancer diagnosis by following a low-fat diet, suggests an analysis from the phase III multicenter randomized Women’s Health Initiative Dietary Modification trial.

Investigators led by Rowan T. Chlebowski, MD, PhD, formerly of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, and now at City of Hope National Medical Center, Duarte, California, analyzed data from 48,835 postmenopausal women who had never had breast cancer and had normal mammograms. The women were randomly assigned 2:3 to a diet aimed at reducing fat intake to 20% of energy and increasing intake of fruits, vegetables, and grains or to a usual diet.