Young age, tumor subtype linked in breast cancer survival

Younger age at diagnosis of breast cancer predicts poor survival only with certain molecular subtypes of tumor, according to a report published online Aug. 1 in the Journal of Clinical Oncology.

An age of 40 years or younger “has long been considered a poor prognostic factor, because young women, on average, have an increased risk of disease recurrence and decreased survival. In recent years, however, with improved understanding of tumor biology, this assertion has been challenged with increased recognition of the prognostic and predictive role of tumor subtype and awareness that young women are more likely to develop more aggressive phenotypes,” said Ann H. Partridge, MD, of the Dana-Farber Cancer Institute, and Brigham and Women’s Hospital, both in Boston, and her associates.

To examine the relationships among patient age, tumor subtypes, and outcomes, they analyzed data for 17,575 women treated at eight U.S. cancer centers in 2000-2007 and enrolled in a National Comprehensive Cancer Network registry. The study participants (mean age, 35 years) all had newly diagnosed unilateral stage I, II, or III breast cancer and were followed for a median of 6.4 years. Their data were stratified by age at diagnosis: 40 years or younger, 41-50 years, 51-60 years, 61-70 years, or over 70 years.

In the initial analysis, younger women were 90% more likely to die of breast cancer than older women. This probability decreased to 50% when the data were adjusted to control for treatment, stage at diagnosis, and tumor grade, then decreased further to 30% when the data were further adjusted to control for tumor molecular subtype and method of detection, the investigators said (J Clin Oncol. 2016 Aug 1; doi:10.1200/JCO.2015.65.8013).

However, when the data were analyzed according to tumor subtype, women who had luminal A breast cancer (7,738 participants) were more than twice as likely to die of their disease if they were aged 40 or younger at diagnosis than if they were older (hazard ratio, 2.1). The age-related increase in risk was slightly lower for luminal B breast cancer (HR, 1.4), and appeared to be largely confined to those with HER2-negative luminal B tumors.

There also was a borderline increased risk of death in younger women who had triple-negative breast cancer (HR, 1.4), compared with older women who had that tumor subtype. In contrast, younger age did not correlate with increased breast cancer mortality among women with HER2-positive disease.

These findings “support the growing evidence that the relationship between age at diagnosis and breast-cancer-specific survival varies by tumor subtype, which has implications for both treatment decisions and future research directions. ....In women with luminal disease, younger age does have a substantial prognostic role, which may reflect inadequate therapy, including lower treatment efficacy and less therapeutic adherence and persistence, as well as residual differences in tumor biology,” Dr. Partridge and her associates said.

No specific source of funding was identified for this study. Dr. Partridge reported serving as a consultant for Pfizer; her associates reported ties to Pfizer, Tokai, Bristol-Myers Squibb, Carevive Systems, Oncothyreon, Amgen, and BeyondSpring Pharmaceuticals.

Younger age at diagnosis of breast cancer predicts poor survival only with certain molecular subtypes of tumor, according to a report published online Aug. 1 in the Journal of Clinical Oncology.

An age of 40 years or younger “has long been considered a poor prognostic factor, because young women, on average, have an increased risk of disease recurrence and decreased survival. In recent years, however, with improved understanding of tumor biology, this assertion has been challenged with increased recognition of the prognostic and predictive role of tumor subtype and awareness that young women are more likely to develop more aggressive phenotypes,” said Ann H. Partridge, MD, of the Dana-Farber Cancer Institute, and Brigham and Women’s Hospital, both in Boston, and her associates.

To examine the relationships among patient age, tumor subtypes, and outcomes, they analyzed data for 17,575 women treated at eight U.S. cancer centers in 2000-2007 and enrolled in a National Comprehensive Cancer Network registry. The study participants (mean age, 35 years) all had newly diagnosed unilateral stage I, II, or III breast cancer and were followed for a median of 6.4 years. Their data were stratified by age at diagnosis: 40 years or younger, 41-50 years, 51-60 years, 61-70 years, or over 70 years.

In the initial analysis, younger women were 90% more likely to die of breast cancer than older women. This probability decreased to 50% when the data were adjusted to control for treatment, stage at diagnosis, and tumor grade, then decreased further to 30% when the data were further adjusted to control for tumor molecular subtype and method of detection, the investigators said (J Clin Oncol. 2016 Aug 1; doi:10.1200/JCO.2015.65.8013).

However, when the data were analyzed according to tumor subtype, women who had luminal A breast cancer (7,738 participants) were more than twice as likely to die of their disease if they were aged 40 or younger at diagnosis than if they were older (hazard ratio, 2.1). The age-related increase in risk was slightly lower for luminal B breast cancer (HR, 1.4), and appeared to be largely confined to those with HER2-negative luminal B tumors.

There also was a borderline increased risk of death in younger women who had triple-negative breast cancer (HR, 1.4), compared with older women who had that tumor subtype. In contrast, younger age did not correlate with increased breast cancer mortality among women with HER2-positive disease.

These findings “support the growing evidence that the relationship between age at diagnosis and breast-cancer-specific survival varies by tumor subtype, which has implications for both treatment decisions and future research directions. ....In women with luminal disease, younger age does have a substantial prognostic role, which may reflect inadequate therapy, including lower treatment efficacy and less therapeutic adherence and persistence, as well as residual differences in tumor biology,” Dr. Partridge and her associates said.

No specific source of funding was identified for this study. Dr. Partridge reported serving as a consultant for Pfizer; her associates reported ties to Pfizer, Tokai, Bristol-Myers Squibb, Carevive Systems, Oncothyreon, Amgen, and BeyondSpring Pharmaceuticals.

Younger age at diagnosis of breast cancer predicts poor survival only with certain molecular subtypes of tumor, according to a report published online Aug. 1 in the Journal of Clinical Oncology.

An age of 40 years or younger “has long been considered a poor prognostic factor, because young women, on average, have an increased risk of disease recurrence and decreased survival. In recent years, however, with improved understanding of tumor biology, this assertion has been challenged with increased recognition of the prognostic and predictive role of tumor subtype and awareness that young women are more likely to develop more aggressive phenotypes,” said Ann H. Partridge, MD, of the Dana-Farber Cancer Institute, and Brigham and Women’s Hospital, both in Boston, and her associates.

To examine the relationships among patient age, tumor subtypes, and outcomes, they analyzed data for 17,575 women treated at eight U.S. cancer centers in 2000-2007 and enrolled in a National Comprehensive Cancer Network registry. The study participants (mean age, 35 years) all had newly diagnosed unilateral stage I, II, or III breast cancer and were followed for a median of 6.4 years. Their data were stratified by age at diagnosis: 40 years or younger, 41-50 years, 51-60 years, 61-70 years, or over 70 years.

In the initial analysis, younger women were 90% more likely to die of breast cancer than older women. This probability decreased to 50% when the data were adjusted to control for treatment, stage at diagnosis, and tumor grade, then decreased further to 30% when the data were further adjusted to control for tumor molecular subtype and method of detection, the investigators said (J Clin Oncol. 2016 Aug 1; doi:10.1200/JCO.2015.65.8013).

However, when the data were analyzed according to tumor subtype, women who had luminal A breast cancer (7,738 participants) were more than twice as likely to die of their disease if they were aged 40 or younger at diagnosis than if they were older (hazard ratio, 2.1). The age-related increase in risk was slightly lower for luminal B breast cancer (HR, 1.4), and appeared to be largely confined to those with HER2-negative luminal B tumors.

There also was a borderline increased risk of death in younger women who had triple-negative breast cancer (HR, 1.4), compared with older women who had that tumor subtype. In contrast, younger age did not correlate with increased breast cancer mortality among women with HER2-positive disease.

These findings “support the growing evidence that the relationship between age at diagnosis and breast-cancer-specific survival varies by tumor subtype, which has implications for both treatment decisions and future research directions. ....In women with luminal disease, younger age does have a substantial prognostic role, which may reflect inadequate therapy, including lower treatment efficacy and less therapeutic adherence and persistence, as well as residual differences in tumor biology,” Dr. Partridge and her associates said.

No specific source of funding was identified for this study. Dr. Partridge reported serving as a consultant for Pfizer; her associates reported ties to Pfizer, Tokai, Bristol-Myers Squibb, Carevive Systems, Oncothyreon, Amgen, and BeyondSpring Pharmaceuticals.