Breast Cancer ICYMI

Key clinical point: Increased stromal tumor-infiltrating lymphocytes (sTIL) were associated with improved survival in young patients (<40 years old) with early-stage, node-negative (N0), triple negative breast cancer (TNBC) who were naive to systemic therapy.

Major finding: At 15 years, the cumulative incidence of distant metastasis or death was only 2.1% (95% CI 0%-5.0%) in patients with high sTIL (≥75%) compared with 38.4% (95% CI 32.1%-44.6%) in patients with low sTIL (<30%), with an increase in overall survival by 19% for every 10% increase in sTIL (adjusted hazard ratio 0.81; 95% CI 0.76-0.87).

Study details: The study evaluated prospectively collected population-based cohort data of 441 patients aged <40 years who had N0 TNBC and had not received neoadjuvant systemic therapy.

Disclosures: This study was supported by The Netherlands Organization for Health Research and Development, A Sister’s Hope, De Vrienden van UMC Utrecht, and other sources. The authors declared serving as consultants, advisors, or in speaker’s bureaus or receiving research grants or travel and accommodation expenses from several sources.

Source: de Jong VMT et al. Prognostic value of stromal tumor-infiltrating lymphocytes in young, node-negative, triple-negative breast cancer patients who did not receive (neo)adjuvant systemic therapy. J Clin Oncol. 2022 (Mar 30). Doi: 10.1200/JCO.21.01536

Key clinical point: Increased stromal tumor-infiltrating lymphocytes (sTIL) were associated with improved survival in young patients (<40 years old) with early-stage, node-negative (N0), triple negative breast cancer (TNBC) who were naive to systemic therapy.

Major finding: At 15 years, the cumulative incidence of distant metastasis or death was only 2.1% (95% CI 0%-5.0%) in patients with high sTIL (≥75%) compared with 38.4% (95% CI 32.1%-44.6%) in patients with low sTIL (<30%), with an increase in overall survival by 19% for every 10% increase in sTIL (adjusted hazard ratio 0.81; 95% CI 0.76-0.87).

Study details: The study evaluated prospectively collected population-based cohort data of 441 patients aged <40 years who had N0 TNBC and had not received neoadjuvant systemic therapy.

Disclosures: This study was supported by The Netherlands Organization for Health Research and Development, A Sister’s Hope, De Vrienden van UMC Utrecht, and other sources. The authors declared serving as consultants, advisors, or in speaker’s bureaus or receiving research grants or travel and accommodation expenses from several sources.

Source: de Jong VMT et al. Prognostic value of stromal tumor-infiltrating lymphocytes in young, node-negative, triple-negative breast cancer patients who did not receive (neo)adjuvant systemic therapy. J Clin Oncol. 2022 (Mar 30). Doi: 10.1200/JCO.21.01536

Key clinical point: Increased stromal tumor-infiltrating lymphocytes (sTIL) were associated with improved survival in young patients (<40 years old) with early-stage, node-negative (N0), triple negative breast cancer (TNBC) who were naive to systemic therapy.

Major finding: At 15 years, the cumulative incidence of distant metastasis or death was only 2.1% (95% CI 0%-5.0%) in patients with high sTIL (≥75%) compared with 38.4% (95% CI 32.1%-44.6%) in patients with low sTIL (<30%), with an increase in overall survival by 19% for every 10% increase in sTIL (adjusted hazard ratio 0.81; 95% CI 0.76-0.87).

Study details: The study evaluated prospectively collected population-based cohort data of 441 patients aged <40 years who had N0 TNBC and had not received neoadjuvant systemic therapy.

Disclosures: This study was supported by The Netherlands Organization for Health Research and Development, A Sister’s Hope, De Vrienden van UMC Utrecht, and other sources. The authors declared serving as consultants, advisors, or in speaker’s bureaus or receiving research grants or travel and accommodation expenses from several sources.

Source: de Jong VMT et al. Prognostic value of stromal tumor-infiltrating lymphocytes in young, node-negative, triple-negative breast cancer patients who did not receive (neo)adjuvant systemic therapy. J Clin Oncol. 2022 (Mar 30). Doi: 10.1200/JCO.21.01536

Key clinical point: Nearly 40% of patients with breast cancer reported severe cancer-related fatigue for up to 4 years after diagnosis, with depression and receipt of hormone therapy being the key risk factors.

Major finding: The estimated risk for severe global fatigue increased from 13.8% at diagnosis to 64.5% at 4 years postdiagnosis in 19% of patients clustered in the deteriorating group, whereas it remained persistently high in 21% of patients clustered in the high-risk group (94.8% at diagnosis and 64.6% at year 4). Depression (P < .001) and receipt of hormonal therapy (P = .0359) were associated with severe global fatigue trajectory.

Study details: This longitudinal analysis of the ongoing prospective CANcer TOxicity trial included 4173 women with stage I, II, or III breast cancer.

Disclosures: This study is supported by Susan G. Komen, Odyssea, French Foundation for Cancer Research, and others. The authors declared serving as consultants, advisory members, or leaders; owning stocks; or receiving honoraria, research funding, or travel and accommodation expenses from several sources.

Source: Vaz-Luis I et al. Long-term longitudinal patterns of patient-reported fatigue after breast cancer: A group-based trajectory analysis. J Clin Oncol. 2022 (Mar 15). Doi: 10.1200/JCO.21.01958

Key clinical point: Nearly 40% of patients with breast cancer reported severe cancer-related fatigue for up to 4 years after diagnosis, with depression and receipt of hormone therapy being the key risk factors.

Major finding: The estimated risk for severe global fatigue increased from 13.8% at diagnosis to 64.5% at 4 years postdiagnosis in 19% of patients clustered in the deteriorating group, whereas it remained persistently high in 21% of patients clustered in the high-risk group (94.8% at diagnosis and 64.6% at year 4). Depression (P < .001) and receipt of hormonal therapy (P = .0359) were associated with severe global fatigue trajectory.

Study details: This longitudinal analysis of the ongoing prospective CANcer TOxicity trial included 4173 women with stage I, II, or III breast cancer.

Disclosures: This study is supported by Susan G. Komen, Odyssea, French Foundation for Cancer Research, and others. The authors declared serving as consultants, advisory members, or leaders; owning stocks; or receiving honoraria, research funding, or travel and accommodation expenses from several sources.

Source: Vaz-Luis I et al. Long-term longitudinal patterns of patient-reported fatigue after breast cancer: A group-based trajectory analysis. J Clin Oncol. 2022 (Mar 15). Doi: 10.1200/JCO.21.01958

Key clinical point: Nearly 40% of patients with breast cancer reported severe cancer-related fatigue for up to 4 years after diagnosis, with depression and receipt of hormone therapy being the key risk factors.

Major finding: The estimated risk for severe global fatigue increased from 13.8% at diagnosis to 64.5% at 4 years postdiagnosis in 19% of patients clustered in the deteriorating group, whereas it remained persistently high in 21% of patients clustered in the high-risk group (94.8% at diagnosis and 64.6% at year 4). Depression (P < .001) and receipt of hormonal therapy (P = .0359) were associated with severe global fatigue trajectory.

Study details: This longitudinal analysis of the ongoing prospective CANcer TOxicity trial included 4173 women with stage I, II, or III breast cancer.

Disclosures: This study is supported by Susan G. Komen, Odyssea, French Foundation for Cancer Research, and others. The authors declared serving as consultants, advisory members, or leaders; owning stocks; or receiving honoraria, research funding, or travel and accommodation expenses from several sources.

Source: Vaz-Luis I et al. Long-term longitudinal patterns of patient-reported fatigue after breast cancer: A group-based trajectory analysis. J Clin Oncol. 2022 (Mar 15). Doi: 10.1200/JCO.21.01958

Key clinical point: Patients with trastuzumab-refractory human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer achieved satisfactory clinical efficacy after switching to lapatinib as the HER2-blockade therapy.

Major finding: After a median follow-up of 33.1 months, patients achieved a median progression free survival (PFS) of 8.5 months, with brain metastases (hazard ratio [HR] 1.582; P = .041) and ≥2 metastatic sites (HR 1.679; P = .007) being independent prognostic markers for PFS. Diarrhea (3.8%) and hand-foot syndrome (9.4%) were the most common grade ≥3 adverse events.

Study details: Findings are from the phase 2 SYSUCC-005 study including 159 women with HER2-positive refractory metastatic breast cancer who rapidly progressed during prior adjuvant/first-line trastuzumab therapy and switched to lapatinib with either capecitabine or vinorelbine.

Disclosures: This study was funded by the Joint Fund of the National Natural Science Foundation of China and Natural Science Foundation of Guangdong Province, among other sources. The authors declared no conflicts of interest.

Source: Duan F et al. The efficacy of human epidermal growth factor receptor 2 (HER2) blockade switching mode in refractory patients with HER2-positive metastatic breast cancer: A phase II, multicenter, single-arm study (SYSUCC-005). BMC Cancer. 2022;22:271 (Mar 15). Doi: 10.1186/s12885-022-09399-2

Key clinical point: Patients with trastuzumab-refractory human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer achieved satisfactory clinical efficacy after switching to lapatinib as the HER2-blockade therapy.

Major finding: After a median follow-up of 33.1 months, patients achieved a median progression free survival (PFS) of 8.5 months, with brain metastases (hazard ratio [HR] 1.582; P = .041) and ≥2 metastatic sites (HR 1.679; P = .007) being independent prognostic markers for PFS. Diarrhea (3.8%) and hand-foot syndrome (9.4%) were the most common grade ≥3 adverse events.

Study details: Findings are from the phase 2 SYSUCC-005 study including 159 women with HER2-positive refractory metastatic breast cancer who rapidly progressed during prior adjuvant/first-line trastuzumab therapy and switched to lapatinib with either capecitabine or vinorelbine.

Disclosures: This study was funded by the Joint Fund of the National Natural Science Foundation of China and Natural Science Foundation of Guangdong Province, among other sources. The authors declared no conflicts of interest.

Source: Duan F et al. The efficacy of human epidermal growth factor receptor 2 (HER2) blockade switching mode in refractory patients with HER2-positive metastatic breast cancer: A phase II, multicenter, single-arm study (SYSUCC-005). BMC Cancer. 2022;22:271 (Mar 15). Doi: 10.1186/s12885-022-09399-2

Key clinical point: Patients with trastuzumab-refractory human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer achieved satisfactory clinical efficacy after switching to lapatinib as the HER2-blockade therapy.

Major finding: After a median follow-up of 33.1 months, patients achieved a median progression free survival (PFS) of 8.5 months, with brain metastases (hazard ratio [HR] 1.582; P = .041) and ≥2 metastatic sites (HR 1.679; P = .007) being independent prognostic markers for PFS. Diarrhea (3.8%) and hand-foot syndrome (9.4%) were the most common grade ≥3 adverse events.

Study details: Findings are from the phase 2 SYSUCC-005 study including 159 women with HER2-positive refractory metastatic breast cancer who rapidly progressed during prior adjuvant/first-line trastuzumab therapy and switched to lapatinib with either capecitabine or vinorelbine.

Disclosures: This study was funded by the Joint Fund of the National Natural Science Foundation of China and Natural Science Foundation of Guangdong Province, among other sources. The authors declared no conflicts of interest.

Source: Duan F et al. The efficacy of human epidermal growth factor receptor 2 (HER2) blockade switching mode in refractory patients with HER2-positive metastatic breast cancer: A phase II, multicenter, single-arm study (SYSUCC-005). BMC Cancer. 2022;22:271 (Mar 15). Doi: 10.1186/s12885-022-09399-2

Key clinical point: Adjuvant abemaciclib plus endocrine therapy (ET) showed a manageable and acceptable safety profile in patients with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-), high-risk, early breast cancer breast cancer.

Major finding: Grade ≥3 adverse events (AE) were more frequent in the abemaciclib+ET vs. ET alone arm (49.7% vs. 16.3%); however, neutropenia, the most frequent grade ≥3 AE, was manageable with dose modification. The discontinuation of abemaciclib and abemaciclib+ET due to AE occurred in 18.5% and 6.5% of patients, respectively, with 66.8% discontinuing abemaciclib because of grade 1/2 AE and <1% because of neutropenia, increased transaminase, interstitial lung disease, or venous thromboembolism.

Study details: Findings are from a safety analysis of the phase 3 monarchE study including 5591 patients with HR+/HER2-, node-positive, high-risk, early breast cancer who received ≥1 dose of abemaciclib+ET or ET alone in the adjuvant setting.

Disclosures: This study was supported by Eli Lilly and Company. Six authors declared being employees or shareholders of Eli Lilly and other authors reported ties with various sources, including Eli Lilly.

Source: Rugo HS et al. Adjuvant abemaciclib combined with endocrine therapy for high risk early breast cancer: Safety and patient-reported outcomes from the monarchE study. Ann Oncol. 2022 (Mar 22). Doi: 10.1016/j.annonc.2022.03.006

Key clinical point: Adjuvant abemaciclib plus endocrine therapy (ET) showed a manageable and acceptable safety profile in patients with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-), high-risk, early breast cancer breast cancer.

Major finding: Grade ≥3 adverse events (AE) were more frequent in the abemaciclib+ET vs. ET alone arm (49.7% vs. 16.3%); however, neutropenia, the most frequent grade ≥3 AE, was manageable with dose modification. The discontinuation of abemaciclib and abemaciclib+ET due to AE occurred in 18.5% and 6.5% of patients, respectively, with 66.8% discontinuing abemaciclib because of grade 1/2 AE and <1% because of neutropenia, increased transaminase, interstitial lung disease, or venous thromboembolism.

Study details: Findings are from a safety analysis of the phase 3 monarchE study including 5591 patients with HR+/HER2-, node-positive, high-risk, early breast cancer who received ≥1 dose of abemaciclib+ET or ET alone in the adjuvant setting.

Disclosures: This study was supported by Eli Lilly and Company. Six authors declared being employees or shareholders of Eli Lilly and other authors reported ties with various sources, including Eli Lilly.

Source: Rugo HS et al. Adjuvant abemaciclib combined with endocrine therapy for high risk early breast cancer: Safety and patient-reported outcomes from the monarchE study. Ann Oncol. 2022 (Mar 22). Doi: 10.1016/j.annonc.2022.03.006

Key clinical point: Adjuvant abemaciclib plus endocrine therapy (ET) showed a manageable and acceptable safety profile in patients with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-), high-risk, early breast cancer breast cancer.

Major finding: Grade ≥3 adverse events (AE) were more frequent in the abemaciclib+ET vs. ET alone arm (49.7% vs. 16.3%); however, neutropenia, the most frequent grade ≥3 AE, was manageable with dose modification. The discontinuation of abemaciclib and abemaciclib+ET due to AE occurred in 18.5% and 6.5% of patients, respectively, with 66.8% discontinuing abemaciclib because of grade 1/2 AE and <1% because of neutropenia, increased transaminase, interstitial lung disease, or venous thromboembolism.

Study details: Findings are from a safety analysis of the phase 3 monarchE study including 5591 patients with HR+/HER2-, node-positive, high-risk, early breast cancer who received ≥1 dose of abemaciclib+ET or ET alone in the adjuvant setting.

Disclosures: This study was supported by Eli Lilly and Company. Six authors declared being employees or shareholders of Eli Lilly and other authors reported ties with various sources, including Eli Lilly.

Source: Rugo HS et al. Adjuvant abemaciclib combined with endocrine therapy for high risk early breast cancer: Safety and patient-reported outcomes from the monarchE study. Ann Oncol. 2022 (Mar 22). Doi: 10.1016/j.annonc.2022.03.006

Key clinical point: Neoadjuvant palbociclib plus endocrine therapy with letrozole and neoadjuvant chemotherapy demonstrated comparable survival outcomes in high-risk patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer.

Major finding: In the neoadjuvant setting, the 3-year progression-free survival (hazard ratio [HR] 1.01; P = .98) and invasive disease-free survival (HR 0.83; P = .71) were not significantly different between the letrozole+palbociclib and chemotherapy groups.

Study details: Findings are from the phase 2 NeoPAL study including 106 postmenopausal women with ER+/HER2-, high-risk, early, luminal B or node-positive luminal A breast cancer who were randomly assigned to receive neoadjuvant letrozole+palbociclib or neoadjuvant chemotherapy.

Disclosures: This study was supported by the French Breast Cancer InterGroup-UNICANCER and Pfizer. Some authors declared serving on advisory boards or receiving funds, honoraria, fees, or personal support from various sources.

Source: Delaloge S et al. Survival outcomes after neoadjuvant letrozole and palbociclib versus third generation chemotherapy for patients with high-risk oestrogen receptor-positive HER2-negative breast cancer. Eur J Cancer. 2022 (Mar 22). Doi: 10.1016/j.ejca.2022.01.014

Key clinical point: Neoadjuvant palbociclib plus endocrine therapy with letrozole and neoadjuvant chemotherapy demonstrated comparable survival outcomes in high-risk patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer.

Major finding: In the neoadjuvant setting, the 3-year progression-free survival (hazard ratio [HR] 1.01; P = .98) and invasive disease-free survival (HR 0.83; P = .71) were not significantly different between the letrozole+palbociclib and chemotherapy groups.

Study details: Findings are from the phase 2 NeoPAL study including 106 postmenopausal women with ER+/HER2-, high-risk, early, luminal B or node-positive luminal A breast cancer who were randomly assigned to receive neoadjuvant letrozole+palbociclib or neoadjuvant chemotherapy.

Disclosures: This study was supported by the French Breast Cancer InterGroup-UNICANCER and Pfizer. Some authors declared serving on advisory boards or receiving funds, honoraria, fees, or personal support from various sources.

Source: Delaloge S et al. Survival outcomes after neoadjuvant letrozole and palbociclib versus third generation chemotherapy for patients with high-risk oestrogen receptor-positive HER2-negative breast cancer. Eur J Cancer. 2022 (Mar 22). Doi: 10.1016/j.ejca.2022.01.014

Key clinical point: Neoadjuvant palbociclib plus endocrine therapy with letrozole and neoadjuvant chemotherapy demonstrated comparable survival outcomes in high-risk patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer.

Major finding: In the neoadjuvant setting, the 3-year progression-free survival (hazard ratio [HR] 1.01; P = .98) and invasive disease-free survival (HR 0.83; P = .71) were not significantly different between the letrozole+palbociclib and chemotherapy groups.

Study details: Findings are from the phase 2 NeoPAL study including 106 postmenopausal women with ER+/HER2-, high-risk, early, luminal B or node-positive luminal A breast cancer who were randomly assigned to receive neoadjuvant letrozole+palbociclib or neoadjuvant chemotherapy.

Disclosures: This study was supported by the French Breast Cancer InterGroup-UNICANCER and Pfizer. Some authors declared serving on advisory boards or receiving funds, honoraria, fees, or personal support from various sources.

Source: Delaloge S et al. Survival outcomes after neoadjuvant letrozole and palbociclib versus third generation chemotherapy for patients with high-risk oestrogen receptor-positive HER2-negative breast cancer. Eur J Cancer. 2022 (Mar 22). Doi: 10.1016/j.ejca.2022.01.014

Key clinical point: Ribociclib plus letrozole vs. letrozole alone prolonged overall survival (OS) by 12.5 months in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer.

Major finding: After a median follow-up of 80 months, ribociclib+letrozole showed significant survival benefit over placebo+letrozole (median overall survival 63.9 vs. 51.4 months; hazard ratio for death 0.76; 2-sided P = .008). No new safety signals were identified.

Study details: Findings are from the phase 3 MONALEESA-2 trial including 668 postmenopausal women with HR+/HER2- recurrent or metastatic breast cancer who had not received prior systemic therapy for advanced disease and were randomly assigned to receive first-line ribociclib or placebo, both with letrozole.

Disclosures: This study was funded by Novartis. Five authors declared being employees or stockholders of Novartis and others reported ties with various sources, including Novartis.

Source: Hortobagyi GN et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med. 2022;386:942-950 (Mar 10). Doi: 10.1056/NEJMoa2114663

Key clinical point: Ribociclib plus letrozole vs. letrozole alone prolonged overall survival (OS) by 12.5 months in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer.

Major finding: After a median follow-up of 80 months, ribociclib+letrozole showed significant survival benefit over placebo+letrozole (median overall survival 63.9 vs. 51.4 months; hazard ratio for death 0.76; 2-sided P = .008). No new safety signals were identified.

Study details: Findings are from the phase 3 MONALEESA-2 trial including 668 postmenopausal women with HR+/HER2- recurrent or metastatic breast cancer who had not received prior systemic therapy for advanced disease and were randomly assigned to receive first-line ribociclib or placebo, both with letrozole.

Disclosures: This study was funded by Novartis. Five authors declared being employees or stockholders of Novartis and others reported ties with various sources, including Novartis.

Source: Hortobagyi GN et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med. 2022;386:942-950 (Mar 10). Doi: 10.1056/NEJMoa2114663

Key clinical point: Ribociclib plus letrozole vs. letrozole alone prolonged overall survival (OS) by 12.5 months in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer.

Major finding: After a median follow-up of 80 months, ribociclib+letrozole showed significant survival benefit over placebo+letrozole (median overall survival 63.9 vs. 51.4 months; hazard ratio for death 0.76; 2-sided P = .008). No new safety signals were identified.

Study details: Findings are from the phase 3 MONALEESA-2 trial including 668 postmenopausal women with HR+/HER2- recurrent or metastatic breast cancer who had not received prior systemic therapy for advanced disease and were randomly assigned to receive first-line ribociclib or placebo, both with letrozole.

Disclosures: This study was funded by Novartis. Five authors declared being employees or stockholders of Novartis and others reported ties with various sources, including Novartis.

Source: Hortobagyi GN et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med. 2022;386:942-950 (Mar 10). Doi: 10.1056/NEJMoa2114663

Key clinical point: Trastuzumab deruxtecan was superior to trastuzumab emtansine in reducing the risk for disease progression or death in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer who had been previously treated with trastuzumab and a taxane.

Major finding: At 12 months, 75.8% of patients in the trastuzumab deruxtecan group vs. 34.1% patients in the trastuzumab emtansine group achieved progression-free survival (hazard ratio for disease progression/death from any cause 0.28; P < .001). The incidence of drug-related adverse events of any grade was 98.1% with trastuzumab deruxtecan and 86.6% with trastuzumab emtansine.

Study details: This interim analysis of the phase 3 DESTINY-Breast03 trial included 524 patients with HER2+ metastatic breast cancer who were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine after their disease progressed having taken trastuzumab and a taxane.

Disclosures: This study was supported by Daiichi Sankyo and AstraZeneca. Four authors declared being employees or stockholders of Daichi Sankyo and one author declared being an employee of AstraZeneca. The other authors reported ties with various sources.

Source: Cortés J et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386:1143-1154 (Mar 24). Doi: 10.1056/NEJMoa2115022

Key clinical point: Trastuzumab deruxtecan was superior to trastuzumab emtansine in reducing the risk for disease progression or death in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer who had been previously treated with trastuzumab and a taxane.

Major finding: At 12 months, 75.8% of patients in the trastuzumab deruxtecan group vs. 34.1% patients in the trastuzumab emtansine group achieved progression-free survival (hazard ratio for disease progression/death from any cause 0.28; P < .001). The incidence of drug-related adverse events of any grade was 98.1% with trastuzumab deruxtecan and 86.6% with trastuzumab emtansine.

Study details: This interim analysis of the phase 3 DESTINY-Breast03 trial included 524 patients with HER2+ metastatic breast cancer who were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine after their disease progressed having taken trastuzumab and a taxane.

Disclosures: This study was supported by Daiichi Sankyo and AstraZeneca. Four authors declared being employees or stockholders of Daichi Sankyo and one author declared being an employee of AstraZeneca. The other authors reported ties with various sources.

Source: Cortés J et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386:1143-1154 (Mar 24). Doi: 10.1056/NEJMoa2115022

Key clinical point: Trastuzumab deruxtecan was superior to trastuzumab emtansine in reducing the risk for disease progression or death in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer who had been previously treated with trastuzumab and a taxane.

Major finding: At 12 months, 75.8% of patients in the trastuzumab deruxtecan group vs. 34.1% patients in the trastuzumab emtansine group achieved progression-free survival (hazard ratio for disease progression/death from any cause 0.28; P < .001). The incidence of drug-related adverse events of any grade was 98.1% with trastuzumab deruxtecan and 86.6% with trastuzumab emtansine.

Study details: This interim analysis of the phase 3 DESTINY-Breast03 trial included 524 patients with HER2+ metastatic breast cancer who were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine after their disease progressed having taken trastuzumab and a taxane.

Disclosures: This study was supported by Daiichi Sankyo and AstraZeneca. Four authors declared being employees or stockholders of Daichi Sankyo and one author declared being an employee of AstraZeneca. The other authors reported ties with various sources.

Source: Cortés J et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386:1143-1154 (Mar 24). Doi: 10.1056/NEJMoa2115022

In more than 10% of cases in which ductal carcinoma in situ (DCIS) recurs in the same breast, the new lesion is genetically distinct from the original lesion, according to a study presented at the annual meeting of the American Association for Cancer Research.

If these findings of de novo tumor recurrences hold true, “it should change how you should treat the patients in the clinic,” commented lead author Tanjina Kader, PhD, a postdoctoral researcher in the department of oncology at the Peter MacCallum Cancer Centre in the University of Melbourne.

Up to a quarter of cases of DCIS recur, and half of those cases emerge in the form of invasive breast cancer. Currently, all recurrent tumor patients are provided the same treatment on the assumption that all recurrences arise from the primary lesion, Dr. Kader commented.

But the new findings could change this practice. If a patient with DCIS returns to the clinic with a tumor independent of the primary lesion, physicians should consider preventive therapies, such as mastectomy or genetic counseling, she said in an interview.

For their study, Dr. Kader and colleagues gathered patient samples and extracted 67 pairs of primary DCIS and their recurrences from the same breast. They also collected 32 samples from nonrecurrent cases of DCIS.

They then used advanced DNA sequencing methods to conduct detailed molecular analyses in order to determine whether the recurrences were genetically distinct from the original lesion.

The team found that 82% of cases appeared to be clonal – derived from the same ancestral cell as the original tumor – and 18% were nonclonal – arose independently of the original DCIS.

The researchers also identified specific genetic changes, including a mutation in the TP53 gene, that were present in recurrences of DCIS but not in nonrecurrent or nonclonal cases.

“It was surprising to see that nonclonal tumors have a similar genetic profile as nonrecurrent tumors,” Dr. Kader said. This means that, if these genetic changes are used as biomarkers to predict the recurrence of DCIS, they could lead to the undertreatment of patients who could develop nonclonal tumors, since these individuals may be categorized as having a low risk of recurrence, she explained.

“For the last 10 years, everyone has been trying their best to find a biomarker without actually taking into account that independent tumors can actually arise on the same breast independently,” Dr. Kader said.

The main limitation of this study was the lack of DNA from matched healthy cells to compare to the patient samples, said Dr. Kader. Because of the lack of these samples, the study focused only on chromosomal changes.

This study is “highly relevant, as it adds to our knowledge to what extent DCIS can be considered a precursor lesion as well as a risk lesion,” said Jelle Wesseling, MD, PhD, a breast pathologist at the Netherlands Cancer Institute. He was not involved in this research, but his team has also found that primary DCIS lesions and their subsequent events can be clonally unrelated.

Dr. Wesseling said there are still many questions, such as whether inherited genetic variants or the tumor microenvironment contribute to DCIS recurrences. “There is a lot more work to be done here to tease this out in more detail.”

The study was funded by grants from the National Breast Cancer Foundation, the Cancer Council Victoria, and the Victorian Cancer Agency.

A version of this article first appeared on Medscape.com.

In more than 10% of cases in which ductal carcinoma in situ (DCIS) recurs in the same breast, the new lesion is genetically distinct from the original lesion, according to a study presented at the annual meeting of the American Association for Cancer Research.

If these findings of de novo tumor recurrences hold true, “it should change how you should treat the patients in the clinic,” commented lead author Tanjina Kader, PhD, a postdoctoral researcher in the department of oncology at the Peter MacCallum Cancer Centre in the University of Melbourne.

Up to a quarter of cases of DCIS recur, and half of those cases emerge in the form of invasive breast cancer. Currently, all recurrent tumor patients are provided the same treatment on the assumption that all recurrences arise from the primary lesion, Dr. Kader commented.

But the new findings could change this practice. If a patient with DCIS returns to the clinic with a tumor independent of the primary lesion, physicians should consider preventive therapies, such as mastectomy or genetic counseling, she said in an interview.

For their study, Dr. Kader and colleagues gathered patient samples and extracted 67 pairs of primary DCIS and their recurrences from the same breast. They also collected 32 samples from nonrecurrent cases of DCIS.

They then used advanced DNA sequencing methods to conduct detailed molecular analyses in order to determine whether the recurrences were genetically distinct from the original lesion.

The team found that 82% of cases appeared to be clonal – derived from the same ancestral cell as the original tumor – and 18% were nonclonal – arose independently of the original DCIS.

The researchers also identified specific genetic changes, including a mutation in the TP53 gene, that were present in recurrences of DCIS but not in nonrecurrent or nonclonal cases.

“It was surprising to see that nonclonal tumors have a similar genetic profile as nonrecurrent tumors,” Dr. Kader said. This means that, if these genetic changes are used as biomarkers to predict the recurrence of DCIS, they could lead to the undertreatment of patients who could develop nonclonal tumors, since these individuals may be categorized as having a low risk of recurrence, she explained.

“For the last 10 years, everyone has been trying their best to find a biomarker without actually taking into account that independent tumors can actually arise on the same breast independently,” Dr. Kader said.

The main limitation of this study was the lack of DNA from matched healthy cells to compare to the patient samples, said Dr. Kader. Because of the lack of these samples, the study focused only on chromosomal changes.

This study is “highly relevant, as it adds to our knowledge to what extent DCIS can be considered a precursor lesion as well as a risk lesion,” said Jelle Wesseling, MD, PhD, a breast pathologist at the Netherlands Cancer Institute. He was not involved in this research, but his team has also found that primary DCIS lesions and their subsequent events can be clonally unrelated.

Dr. Wesseling said there are still many questions, such as whether inherited genetic variants or the tumor microenvironment contribute to DCIS recurrences. “There is a lot more work to be done here to tease this out in more detail.”

The study was funded by grants from the National Breast Cancer Foundation, the Cancer Council Victoria, and the Victorian Cancer Agency.

A version of this article first appeared on Medscape.com.

In more than 10% of cases in which ductal carcinoma in situ (DCIS) recurs in the same breast, the new lesion is genetically distinct from the original lesion, according to a study presented at the annual meeting of the American Association for Cancer Research.

If these findings of de novo tumor recurrences hold true, “it should change how you should treat the patients in the clinic,” commented lead author Tanjina Kader, PhD, a postdoctoral researcher in the department of oncology at the Peter MacCallum Cancer Centre in the University of Melbourne.

Up to a quarter of cases of DCIS recur, and half of those cases emerge in the form of invasive breast cancer. Currently, all recurrent tumor patients are provided the same treatment on the assumption that all recurrences arise from the primary lesion, Dr. Kader commented.

But the new findings could change this practice. If a patient with DCIS returns to the clinic with a tumor independent of the primary lesion, physicians should consider preventive therapies, such as mastectomy or genetic counseling, she said in an interview.

For their study, Dr. Kader and colleagues gathered patient samples and extracted 67 pairs of primary DCIS and their recurrences from the same breast. They also collected 32 samples from nonrecurrent cases of DCIS.

They then used advanced DNA sequencing methods to conduct detailed molecular analyses in order to determine whether the recurrences were genetically distinct from the original lesion.

The team found that 82% of cases appeared to be clonal – derived from the same ancestral cell as the original tumor – and 18% were nonclonal – arose independently of the original DCIS.

The researchers also identified specific genetic changes, including a mutation in the TP53 gene, that were present in recurrences of DCIS but not in nonrecurrent or nonclonal cases.

“It was surprising to see that nonclonal tumors have a similar genetic profile as nonrecurrent tumors,” Dr. Kader said. This means that, if these genetic changes are used as biomarkers to predict the recurrence of DCIS, they could lead to the undertreatment of patients who could develop nonclonal tumors, since these individuals may be categorized as having a low risk of recurrence, she explained.

“For the last 10 years, everyone has been trying their best to find a biomarker without actually taking into account that independent tumors can actually arise on the same breast independently,” Dr. Kader said.

The main limitation of this study was the lack of DNA from matched healthy cells to compare to the patient samples, said Dr. Kader. Because of the lack of these samples, the study focused only on chromosomal changes.

This study is “highly relevant, as it adds to our knowledge to what extent DCIS can be considered a precursor lesion as well as a risk lesion,” said Jelle Wesseling, MD, PhD, a breast pathologist at the Netherlands Cancer Institute. He was not involved in this research, but his team has also found that primary DCIS lesions and their subsequent events can be clonally unrelated.

Dr. Wesseling said there are still many questions, such as whether inherited genetic variants or the tumor microenvironment contribute to DCIS recurrences. “There is a lot more work to be done here to tease this out in more detail.”

The study was funded by grants from the National Breast Cancer Foundation, the Cancer Council Victoria, and the Victorian Cancer Agency.

A version of this article first appeared on Medscape.com.

Extraverts and individuals who are disciplined are less likely to experience cognitive decline later in life, whereas those with neuroticism have an increased risk for cognitive dysfunction, new research shows.

Investigators analyzed data from almost 2,000 individuals enrolled in the Rush Memory and Aging Project (MAP) – a longitudinal study of older adults living in the greater Chicago metropolitan region and northeastern Illinois – with recruitment that began in 1997 and continues through today. Participants received a personality assessment as well as annual assessments of their cognitive abilities.

Those with high scores on measures of conscientiousness were significantly less likely to progress from normal cognition to mild cognitive impairment (MCI) during the study. In fact, scoring an extra 1 standard deviation on the conscientiousness scale was associated with a 22% lower risk of transitioning from no cognitive impairment (NCI) to MCI. On the other hand, scoring an additional 1 SD on a neuroticism scale was associated with a 12% increased risk of transitioning to MCI.

Participants who scored high on extraversion, as well as those who scored high on conscientiousness or low on neuroticism, tended to maintain normal cognitive functioning longer than other participants.

“Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan,” lead author Tomiko Yoneda, PhD, a postdoctoral researcher in the department of medical social sciences, Northwestern University, Chicago, said in an interview.

“The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes,” she added.

The study was published online in the Journal of Personality and Social Psychology.
 

Competing risk factors

Personality traits “reflect an individual’s persistent patterns of thinking, feeling, and behaving,” Dr. Yoneda said.

“For example, conscientiousness is characterized by competence, dutifulness, and self-discipline, while neuroticism is characterized by anxiety, depressive symptoms, and emotional instability. Likewise, individuals high in extraversion tend to be enthusiastic, gregarious, talkative, and assertive,” she added.

Previous research “suggests that low conscientiousness and high neuroticism are associated with an increased risk of cognitive impairment,” she continued. However, “there is also an increased risk of death in older adulthood – in other words, these outcomes are ‘competing risk factors.’”

Dr. Yoneda said her team wanted to “examine the impact of personality traits on the simultaneous risk of transitioning to mild cognitive impairment, dementia, and death.”  

For the study, the researchers analyzed data from 1,954 participants in MAP (mean age at baseline 80 years, 73.7% female, 86.8% White), who received a personality assessment and annual assessments of their cognitive abilities.

To assess personality traits – in particular, conscientiousness, neuroticism, and extraversion – the researchers used the NEO Five Factor Inventory (NEO-FFI). They also used multistate survival modeling to examine the potential association between these traits and transitions from one cognitive status category to another (NCI, MCI, and dementia) and to death.
 

Cognitive healthspan

By the end of the study, over half of the sample (54%) had died.

Most transitions showed “relative stability in cognitive status across measurement occasions.”

• NCI to NCI (n = 7,368)
• MCI to MCI (n = 1,244)
• Dementia to dementia (n = 876)

There were 725 “backward transitions” from MCI to NCI, “which may reflect improvement or within-person variability in cognitive functioning, or learning effects,” the authors note.

There were only 114 “backward transitions” from dementia to MCI and only 12 from dementia to NCI, “suggesting that improvement in cognitive status was relatively rare, particularly once an individual progresses to dementia.”

After adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4 allele, the researchers found that personality traits were the most important factors in the transition from NCI to MCI.

Higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI (hazard ratio, 0.78; 95% confidence interval, 0.72-0.85). Conversely, higher neuroticism was associated with an increased risk of transitioning from NCI to MCI (HR, 1.12; 95% CI, 1.04-1.21) and a significantly decreased likelihood of transition back from MCI to NCI (HR, 0.90; 95% CI, 0.81-1.00).

Scoring ~6 points on a conscientiousness scale ranging from 0-48 (that is, 1 SD on the scale) was significantly associated with ~22% lower risk of transitioning forward from NCI to MCI, while scoring ~7 more points on a neuroticism scale (1 SD) was significantly associated with ~12% higher risk of transitioning from NCI to MCI.

Higher extraversion was associated with an increased likelihood of transitioning from MCI back to NCI (HR, 1.12; 95% CI, 1.03-1.22), and although extraversion was not associated with a longer total lifespan, participants who scored high on extraversion, as well as those who scored low on conscientiousness or low on neuroticism, maintained normal cognitive function longer than other participants.

“Our results suggest that high conscientiousness and low neuroticism may protect individuals against mild cognitive impairment,” said Dr. Yoneda.

Importantly, individuals who were either higher in conscientiousness, higher in extraversion, or lower in neuroticism had more years of “cognitive healthspan,” meaning more years without cognitive impairment,” she added.

In addition, “individuals lower in neuroticism and higher in extraversion were more likely to recover after receiving an MCI diagnosis, suggesting that these traits may be protective even after an individual starts to progress to dementia,” she said.

The authors note that the study focused on only three of the Big Five personality traits, while the other 2 – openness to experience and agreeableness – may also be associated with cognitive aging processes and mortality.

Nevertheless, given the current results, alongside extensive research in the personality field, aiming to increase conscientiousness through persistent behavioral change is one potential strategy for promoting healthy cognitive aging, Dr. Yoneda said.
 

‘Invaluable window’

In a comment, Brent Roberts, PhD, professor of psychology, University of Illinois Urbana-Champaign, said the study provides an “invaluable window into how personality affects the process of decline and either accelerates it, as in the role of neuroticism, or decelerates it, as in the role of conscientiousness.”

“I think the most fascinating finding was the fact that extraversion was related to transitioning from MCI back to NCI. These types of transitions have simply not been part of prior research, and it provides utterly unique insights and opportunities for interventions that may actually help people recover from a decline,” said Dr. Roberts, who was not involved in the research.

Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, called the paper “novel” because it investigated the transitions between normal cognition and mild impairment and between mild impairment and dementia.

Dr. Sexton, who was associated with this research team, cautioned that is it observational, “so it can illuminate associations or correlations, but not causes. As a result, we can’t say for sure what the mechanisms are behind these potential connections between personality and cognition, and more research is needed.”

The research was supported by the Alzheimer Society Research Program, Social Sciences and Humanities Research Council, and the National Institute on Aging of the National Institutes of Health. Dr. Yoneda and co-authors, Dr. Roberts, and Dr. Sexton have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Extraverts and individuals who are disciplined are less likely to experience cognitive decline later in life, whereas those with neuroticism have an increased risk for cognitive dysfunction, new research shows.

Investigators analyzed data from almost 2,000 individuals enrolled in the Rush Memory and Aging Project (MAP) – a longitudinal study of older adults living in the greater Chicago metropolitan region and northeastern Illinois – with recruitment that began in 1997 and continues through today. Participants received a personality assessment as well as annual assessments of their cognitive abilities.

Those with high scores on measures of conscientiousness were significantly less likely to progress from normal cognition to mild cognitive impairment (MCI) during the study. In fact, scoring an extra 1 standard deviation on the conscientiousness scale was associated with a 22% lower risk of transitioning from no cognitive impairment (NCI) to MCI. On the other hand, scoring an additional 1 SD on a neuroticism scale was associated with a 12% increased risk of transitioning to MCI.

Participants who scored high on extraversion, as well as those who scored high on conscientiousness or low on neuroticism, tended to maintain normal cognitive functioning longer than other participants.

“Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan,” lead author Tomiko Yoneda, PhD, a postdoctoral researcher in the department of medical social sciences, Northwestern University, Chicago, said in an interview.

“The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes,” she added.

The study was published online in the Journal of Personality and Social Psychology.
 

Competing risk factors

Personality traits “reflect an individual’s persistent patterns of thinking, feeling, and behaving,” Dr. Yoneda said.

“For example, conscientiousness is characterized by competence, dutifulness, and self-discipline, while neuroticism is characterized by anxiety, depressive symptoms, and emotional instability. Likewise, individuals high in extraversion tend to be enthusiastic, gregarious, talkative, and assertive,” she added.

Previous research “suggests that low conscientiousness and high neuroticism are associated with an increased risk of cognitive impairment,” she continued. However, “there is also an increased risk of death in older adulthood – in other words, these outcomes are ‘competing risk factors.’”

Dr. Yoneda said her team wanted to “examine the impact of personality traits on the simultaneous risk of transitioning to mild cognitive impairment, dementia, and death.”  

For the study, the researchers analyzed data from 1,954 participants in MAP (mean age at baseline 80 years, 73.7% female, 86.8% White), who received a personality assessment and annual assessments of their cognitive abilities.

To assess personality traits – in particular, conscientiousness, neuroticism, and extraversion – the researchers used the NEO Five Factor Inventory (NEO-FFI). They also used multistate survival modeling to examine the potential association between these traits and transitions from one cognitive status category to another (NCI, MCI, and dementia) and to death.
 

Cognitive healthspan

By the end of the study, over half of the sample (54%) had died.

Most transitions showed “relative stability in cognitive status across measurement occasions.”

• NCI to NCI (n = 7,368)
• MCI to MCI (n = 1,244)
• Dementia to dementia (n = 876)

There were 725 “backward transitions” from MCI to NCI, “which may reflect improvement or within-person variability in cognitive functioning, or learning effects,” the authors note.

There were only 114 “backward transitions” from dementia to MCI and only 12 from dementia to NCI, “suggesting that improvement in cognitive status was relatively rare, particularly once an individual progresses to dementia.”

After adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4 allele, the researchers found that personality traits were the most important factors in the transition from NCI to MCI.

Higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI (hazard ratio, 0.78; 95% confidence interval, 0.72-0.85). Conversely, higher neuroticism was associated with an increased risk of transitioning from NCI to MCI (HR, 1.12; 95% CI, 1.04-1.21) and a significantly decreased likelihood of transition back from MCI to NCI (HR, 0.90; 95% CI, 0.81-1.00).

Scoring ~6 points on a conscientiousness scale ranging from 0-48 (that is, 1 SD on the scale) was significantly associated with ~22% lower risk of transitioning forward from NCI to MCI, while scoring ~7 more points on a neuroticism scale (1 SD) was significantly associated with ~12% higher risk of transitioning from NCI to MCI.

Higher extraversion was associated with an increased likelihood of transitioning from MCI back to NCI (HR, 1.12; 95% CI, 1.03-1.22), and although extraversion was not associated with a longer total lifespan, participants who scored high on extraversion, as well as those who scored low on conscientiousness or low on neuroticism, maintained normal cognitive function longer than other participants.

“Our results suggest that high conscientiousness and low neuroticism may protect individuals against mild cognitive impairment,” said Dr. Yoneda.

Importantly, individuals who were either higher in conscientiousness, higher in extraversion, or lower in neuroticism had more years of “cognitive healthspan,” meaning more years without cognitive impairment,” she added.

In addition, “individuals lower in neuroticism and higher in extraversion were more likely to recover after receiving an MCI diagnosis, suggesting that these traits may be protective even after an individual starts to progress to dementia,” she said.

The authors note that the study focused on only three of the Big Five personality traits, while the other 2 – openness to experience and agreeableness – may also be associated with cognitive aging processes and mortality.

Nevertheless, given the current results, alongside extensive research in the personality field, aiming to increase conscientiousness through persistent behavioral change is one potential strategy for promoting healthy cognitive aging, Dr. Yoneda said.
 

‘Invaluable window’

In a comment, Brent Roberts, PhD, professor of psychology, University of Illinois Urbana-Champaign, said the study provides an “invaluable window into how personality affects the process of decline and either accelerates it, as in the role of neuroticism, or decelerates it, as in the role of conscientiousness.”

“I think the most fascinating finding was the fact that extraversion was related to transitioning from MCI back to NCI. These types of transitions have simply not been part of prior research, and it provides utterly unique insights and opportunities for interventions that may actually help people recover from a decline,” said Dr. Roberts, who was not involved in the research.

Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, called the paper “novel” because it investigated the transitions between normal cognition and mild impairment and between mild impairment and dementia.

Dr. Sexton, who was associated with this research team, cautioned that is it observational, “so it can illuminate associations or correlations, but not causes. As a result, we can’t say for sure what the mechanisms are behind these potential connections between personality and cognition, and more research is needed.”

The research was supported by the Alzheimer Society Research Program, Social Sciences and Humanities Research Council, and the National Institute on Aging of the National Institutes of Health. Dr. Yoneda and co-authors, Dr. Roberts, and Dr. Sexton have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Extraverts and individuals who are disciplined are less likely to experience cognitive decline later in life, whereas those with neuroticism have an increased risk for cognitive dysfunction, new research shows.

Investigators analyzed data from almost 2,000 individuals enrolled in the Rush Memory and Aging Project (MAP) – a longitudinal study of older adults living in the greater Chicago metropolitan region and northeastern Illinois – with recruitment that began in 1997 and continues through today. Participants received a personality assessment as well as annual assessments of their cognitive abilities.

Those with high scores on measures of conscientiousness were significantly less likely to progress from normal cognition to mild cognitive impairment (MCI) during the study. In fact, scoring an extra 1 standard deviation on the conscientiousness scale was associated with a 22% lower risk of transitioning from no cognitive impairment (NCI) to MCI. On the other hand, scoring an additional 1 SD on a neuroticism scale was associated with a 12% increased risk of transitioning to MCI.

Participants who scored high on extraversion, as well as those who scored high on conscientiousness or low on neuroticism, tended to maintain normal cognitive functioning longer than other participants.

“Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan,” lead author Tomiko Yoneda, PhD, a postdoctoral researcher in the department of medical social sciences, Northwestern University, Chicago, said in an interview.

“The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes,” she added.

The study was published online in the Journal of Personality and Social Psychology.
 

Competing risk factors

Personality traits “reflect an individual’s persistent patterns of thinking, feeling, and behaving,” Dr. Yoneda said.

“For example, conscientiousness is characterized by competence, dutifulness, and self-discipline, while neuroticism is characterized by anxiety, depressive symptoms, and emotional instability. Likewise, individuals high in extraversion tend to be enthusiastic, gregarious, talkative, and assertive,” she added.

Previous research “suggests that low conscientiousness and high neuroticism are associated with an increased risk of cognitive impairment,” she continued. However, “there is also an increased risk of death in older adulthood – in other words, these outcomes are ‘competing risk factors.’”

Dr. Yoneda said her team wanted to “examine the impact of personality traits on the simultaneous risk of transitioning to mild cognitive impairment, dementia, and death.”  

For the study, the researchers analyzed data from 1,954 participants in MAP (mean age at baseline 80 years, 73.7% female, 86.8% White), who received a personality assessment and annual assessments of their cognitive abilities.

To assess personality traits – in particular, conscientiousness, neuroticism, and extraversion – the researchers used the NEO Five Factor Inventory (NEO-FFI). They also used multistate survival modeling to examine the potential association between these traits and transitions from one cognitive status category to another (NCI, MCI, and dementia) and to death.
 

Cognitive healthspan

By the end of the study, over half of the sample (54%) had died.

Most transitions showed “relative stability in cognitive status across measurement occasions.”

• NCI to NCI (n = 7,368)
• MCI to MCI (n = 1,244)
• Dementia to dementia (n = 876)

There were 725 “backward transitions” from MCI to NCI, “which may reflect improvement or within-person variability in cognitive functioning, or learning effects,” the authors note.

There were only 114 “backward transitions” from dementia to MCI and only 12 from dementia to NCI, “suggesting that improvement in cognitive status was relatively rare, particularly once an individual progresses to dementia.”

After adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4 allele, the researchers found that personality traits were the most important factors in the transition from NCI to MCI.

Higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI (hazard ratio, 0.78; 95% confidence interval, 0.72-0.85). Conversely, higher neuroticism was associated with an increased risk of transitioning from NCI to MCI (HR, 1.12; 95% CI, 1.04-1.21) and a significantly decreased likelihood of transition back from MCI to NCI (HR, 0.90; 95% CI, 0.81-1.00).

Scoring ~6 points on a conscientiousness scale ranging from 0-48 (that is, 1 SD on the scale) was significantly associated with ~22% lower risk of transitioning forward from NCI to MCI, while scoring ~7 more points on a neuroticism scale (1 SD) was significantly associated with ~12% higher risk of transitioning from NCI to MCI.

Higher extraversion was associated with an increased likelihood of transitioning from MCI back to NCI (HR, 1.12; 95% CI, 1.03-1.22), and although extraversion was not associated with a longer total lifespan, participants who scored high on extraversion, as well as those who scored low on conscientiousness or low on neuroticism, maintained normal cognitive function longer than other participants.

“Our results suggest that high conscientiousness and low neuroticism may protect individuals against mild cognitive impairment,” said Dr. Yoneda.

Importantly, individuals who were either higher in conscientiousness, higher in extraversion, or lower in neuroticism had more years of “cognitive healthspan,” meaning more years without cognitive impairment,” she added.

In addition, “individuals lower in neuroticism and higher in extraversion were more likely to recover after receiving an MCI diagnosis, suggesting that these traits may be protective even after an individual starts to progress to dementia,” she said.

The authors note that the study focused on only three of the Big Five personality traits, while the other 2 – openness to experience and agreeableness – may also be associated with cognitive aging processes and mortality.

Nevertheless, given the current results, alongside extensive research in the personality field, aiming to increase conscientiousness through persistent behavioral change is one potential strategy for promoting healthy cognitive aging, Dr. Yoneda said.
 

‘Invaluable window’

In a comment, Brent Roberts, PhD, professor of psychology, University of Illinois Urbana-Champaign, said the study provides an “invaluable window into how personality affects the process of decline and either accelerates it, as in the role of neuroticism, or decelerates it, as in the role of conscientiousness.”

“I think the most fascinating finding was the fact that extraversion was related to transitioning from MCI back to NCI. These types of transitions have simply not been part of prior research, and it provides utterly unique insights and opportunities for interventions that may actually help people recover from a decline,” said Dr. Roberts, who was not involved in the research.

Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, called the paper “novel” because it investigated the transitions between normal cognition and mild impairment and between mild impairment and dementia.

Dr. Sexton, who was associated with this research team, cautioned that is it observational, “so it can illuminate associations or correlations, but not causes. As a result, we can’t say for sure what the mechanisms are behind these potential connections between personality and cognition, and more research is needed.”

The research was supported by the Alzheimer Society Research Program, Social Sciences and Humanities Research Council, and the National Institute on Aging of the National Institutes of Health. Dr. Yoneda and co-authors, Dr. Roberts, and Dr. Sexton have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women diagnosed with early breast cancer facing surgery often have a choice of having all of their breast or only a part of the breast removed.

A new study shows that a patient’s satisfaction with their breasts at 10 years after surgery is similar for both groups of women.

However, superior psychosocial and sexual well-being at 10 years after surgery was reported by women who underwent breast-conserving surgery and adjuvant radiation therapy (RT), compared with those who underwent mastectomy and reconstruction.

“These findings may inform preference-sensitive decision-making for women with early-stage breast cancer,” write the authors, led by Benjamin D. Smith, MD, department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston.

The study was published online in JAMA Surgery.

These findings have important implications for patient decision-making, given that more women eligible for breast-conserving surgery are opting for a mastectomy, say Sudheer Vemuru, MD, from the University of Colorado at Denver, Aurora, and colleagues, writing in an accompanying editorial.

“Overall, the preponderance of evidence suggests superior short-term and long-term patient-reported outcomes in patients with early-stage breast cancer undergoing breast conserving surgery compared with mastectomy,” they comment.
 

Study details

For their study, Dr. Smith and colleagues conducted a comparative effectiveness research study using data from the Texas Cancer Registry and identified women diagnosed with stage 0-II breast cancer and treated with breast-conserving surgery or mastectomy and reconstruction between 2006 and 2008.

A total of 647 patients were included in their analysis (40%; 356 had undergone breast-conserving surgery; 291 had undergone mastectomy and reconstruction), 551 (85.2%) confirmed treatment with breast-conserving surgery with RT (n = 315) or mastectomy and reconstruction without RT (n = 236).

The median age of the cohort was 53 years and the median time from diagnosis to survey was 10.3 years. Mastectomy and reconstruction were more common among women who were White, younger, node positive, had larger tumors, had bilateral breast cancer, received chemotherapy, and had higher income.

The primary outcome was patient satisfaction with their breasts, as measured with the BREAST-Q patient-reported outcome measure. Secondary outcomes included physical well-being, psychosocial well-being, and sexual well-being. The EuroQol Health-Related Quality of Life 5-Dimension, 3-Level gaged health utility, and local therapy decisional regret was measured via the Decisional Regret Scale.

Using breast-conserving surgery plus RT as the referent, the authors did not find any significant differences in breast satisfaction, physical well-being, health utility, or decisional regret among the study cohorts: breast satisfaction: effect size, 2.71 (P = .30); physical well-being: effect size, –1.80 (P = .36); health utility: effect size, –0.003 (P = .83); and decisional regret: effect size, 1.32 (P = .61).

However, psychosocial well-being (effect size, –8.61; P < .001) and sexual well-being (effect size, –10.68; P < .001) were significantly worse among women who had undergone mastectomy and reconstruction without RT.

They noted that interactions of race and ethnicity and age by treatment group were not significant for reported satisfaction with breast outcomes. But the findings “indicated that the burden of poor long-term QOL outcomes was greater among younger individuals, those with lower educational attainment and income, and certain racial and ethnic minority populations,” they write. “These findings suggest that opportunities exist to enhance equity in the long-term QOL of individuals with breast cancer.”

The editorialists note that previous studies have also found diminished quality of life following mastectomy compared with breast-conserving surgery. However, most of these prior studies included patients undergoing breast-conserving surgery without RT, patients undergoing mastectomy without reconstruction, and patients undergoing mastectomy with RT.

In contrast, this latest study “directly compared breast-conserving surgery with RT vs. mastectomy and reconstruction without RT to avoid those potential confounders,” they point out.

The study was supported by grants from the National Cancer Institute and other bodies. Several of the study authors disclosed relationships with industry and/or with nonprofit organizations. The full list can be found with the original article. Editorialist Clara Lee, MD, reported receiving grants from the Agency for Healthcare Research and Quality during the conduct of the study.

A version of this article first appeared on Medscape.com.

Women diagnosed with early breast cancer facing surgery often have a choice of having all of their breast or only a part of the breast removed.

A new study shows that a patient’s satisfaction with their breasts at 10 years after surgery is similar for both groups of women.

However, superior psychosocial and sexual well-being at 10 years after surgery was reported by women who underwent breast-conserving surgery and adjuvant radiation therapy (RT), compared with those who underwent mastectomy and reconstruction.

“These findings may inform preference-sensitive decision-making for women with early-stage breast cancer,” write the authors, led by Benjamin D. Smith, MD, department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston.

The study was published online in JAMA Surgery.

These findings have important implications for patient decision-making, given that more women eligible for breast-conserving surgery are opting for a mastectomy, say Sudheer Vemuru, MD, from the University of Colorado at Denver, Aurora, and colleagues, writing in an accompanying editorial.

“Overall, the preponderance of evidence suggests superior short-term and long-term patient-reported outcomes in patients with early-stage breast cancer undergoing breast conserving surgery compared with mastectomy,” they comment.
 

Study details

For their study, Dr. Smith and colleagues conducted a comparative effectiveness research study using data from the Texas Cancer Registry and identified women diagnosed with stage 0-II breast cancer and treated with breast-conserving surgery or mastectomy and reconstruction between 2006 and 2008.

A total of 647 patients were included in their analysis (40%; 356 had undergone breast-conserving surgery; 291 had undergone mastectomy and reconstruction), 551 (85.2%) confirmed treatment with breast-conserving surgery with RT (n = 315) or mastectomy and reconstruction without RT (n = 236).

The median age of the cohort was 53 years and the median time from diagnosis to survey was 10.3 years. Mastectomy and reconstruction were more common among women who were White, younger, node positive, had larger tumors, had bilateral breast cancer, received chemotherapy, and had higher income.

The primary outcome was patient satisfaction with their breasts, as measured with the BREAST-Q patient-reported outcome measure. Secondary outcomes included physical well-being, psychosocial well-being, and sexual well-being. The EuroQol Health-Related Quality of Life 5-Dimension, 3-Level gaged health utility, and local therapy decisional regret was measured via the Decisional Regret Scale.

Using breast-conserving surgery plus RT as the referent, the authors did not find any significant differences in breast satisfaction, physical well-being, health utility, or decisional regret among the study cohorts: breast satisfaction: effect size, 2.71 (P = .30); physical well-being: effect size, –1.80 (P = .36); health utility: effect size, –0.003 (P = .83); and decisional regret: effect size, 1.32 (P = .61).

However, psychosocial well-being (effect size, –8.61; P < .001) and sexual well-being (effect size, –10.68; P < .001) were significantly worse among women who had undergone mastectomy and reconstruction without RT.

They noted that interactions of race and ethnicity and age by treatment group were not significant for reported satisfaction with breast outcomes. But the findings “indicated that the burden of poor long-term QOL outcomes was greater among younger individuals, those with lower educational attainment and income, and certain racial and ethnic minority populations,” they write. “These findings suggest that opportunities exist to enhance equity in the long-term QOL of individuals with breast cancer.”

The editorialists note that previous studies have also found diminished quality of life following mastectomy compared with breast-conserving surgery. However, most of these prior studies included patients undergoing breast-conserving surgery without RT, patients undergoing mastectomy without reconstruction, and patients undergoing mastectomy with RT.

In contrast, this latest study “directly compared breast-conserving surgery with RT vs. mastectomy and reconstruction without RT to avoid those potential confounders,” they point out.

The study was supported by grants from the National Cancer Institute and other bodies. Several of the study authors disclosed relationships with industry and/or with nonprofit organizations. The full list can be found with the original article. Editorialist Clara Lee, MD, reported receiving grants from the Agency for Healthcare Research and Quality during the conduct of the study.

A version of this article first appeared on Medscape.com.

Women diagnosed with early breast cancer facing surgery often have a choice of having all of their breast or only a part of the breast removed.

A new study shows that a patient’s satisfaction with their breasts at 10 years after surgery is similar for both groups of women.

However, superior psychosocial and sexual well-being at 10 years after surgery was reported by women who underwent breast-conserving surgery and adjuvant radiation therapy (RT), compared with those who underwent mastectomy and reconstruction.

“These findings may inform preference-sensitive decision-making for women with early-stage breast cancer,” write the authors, led by Benjamin D. Smith, MD, department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston.

The study was published online in JAMA Surgery.

These findings have important implications for patient decision-making, given that more women eligible for breast-conserving surgery are opting for a mastectomy, say Sudheer Vemuru, MD, from the University of Colorado at Denver, Aurora, and colleagues, writing in an accompanying editorial.

“Overall, the preponderance of evidence suggests superior short-term and long-term patient-reported outcomes in patients with early-stage breast cancer undergoing breast conserving surgery compared with mastectomy,” they comment.
 

Study details

For their study, Dr. Smith and colleagues conducted a comparative effectiveness research study using data from the Texas Cancer Registry and identified women diagnosed with stage 0-II breast cancer and treated with breast-conserving surgery or mastectomy and reconstruction between 2006 and 2008.

A total of 647 patients were included in their analysis (40%; 356 had undergone breast-conserving surgery; 291 had undergone mastectomy and reconstruction), 551 (85.2%) confirmed treatment with breast-conserving surgery with RT (n = 315) or mastectomy and reconstruction without RT (n = 236).

The median age of the cohort was 53 years and the median time from diagnosis to survey was 10.3 years. Mastectomy and reconstruction were more common among women who were White, younger, node positive, had larger tumors, had bilateral breast cancer, received chemotherapy, and had higher income.

The primary outcome was patient satisfaction with their breasts, as measured with the BREAST-Q patient-reported outcome measure. Secondary outcomes included physical well-being, psychosocial well-being, and sexual well-being. The EuroQol Health-Related Quality of Life 5-Dimension, 3-Level gaged health utility, and local therapy decisional regret was measured via the Decisional Regret Scale.

Using breast-conserving surgery plus RT as the referent, the authors did not find any significant differences in breast satisfaction, physical well-being, health utility, or decisional regret among the study cohorts: breast satisfaction: effect size, 2.71 (P = .30); physical well-being: effect size, –1.80 (P = .36); health utility: effect size, –0.003 (P = .83); and decisional regret: effect size, 1.32 (P = .61).

However, psychosocial well-being (effect size, –8.61; P < .001) and sexual well-being (effect size, –10.68; P < .001) were significantly worse among women who had undergone mastectomy and reconstruction without RT.

They noted that interactions of race and ethnicity and age by treatment group were not significant for reported satisfaction with breast outcomes. But the findings “indicated that the burden of poor long-term QOL outcomes was greater among younger individuals, those with lower educational attainment and income, and certain racial and ethnic minority populations,” they write. “These findings suggest that opportunities exist to enhance equity in the long-term QOL of individuals with breast cancer.”

The editorialists note that previous studies have also found diminished quality of life following mastectomy compared with breast-conserving surgery. However, most of these prior studies included patients undergoing breast-conserving surgery without RT, patients undergoing mastectomy without reconstruction, and patients undergoing mastectomy with RT.

In contrast, this latest study “directly compared breast-conserving surgery with RT vs. mastectomy and reconstruction without RT to avoid those potential confounders,” they point out.

The study was supported by grants from the National Cancer Institute and other bodies. Several of the study authors disclosed relationships with industry and/or with nonprofit organizations. The full list can be found with the original article. Editorialist Clara Lee, MD, reported receiving grants from the Agency for Healthcare Research and Quality during the conduct of the study.

A version of this article first appeared on Medscape.com.