Key clinical point: According to an analysis of two large prospective US-based cohorts, the consumption of olive oil was not associated with an increased risk for breast cancer (BC) among women.

Major finding: Compared with women who never or rarely consumed olive oil, those with the highest consumption of olive oil (>1/2 tablespoon/day or >7 g/day) did not report an increased risk of developing BC (hazard ratio 1.01;  95% CI 0.93-1.09).

Study details: Findings are from an analysis of two large prospective cohorts of women who were free of cancer at baseline, the Nurses’ Health Study (n = 71,330) and Nurses’ Health Study II (n = 93,295), of whom 9638 women developed invasive BC after 3,744,068 person-years of follow-up.

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors declared no conflicts of interest.

Source: Romanos-Nanclares A et al. Consumption of olive oil and risk of breast cancer in U.S. women: Results from the Nurses' Health Studies. Br J Cancer. 2023 (Jun 13). Doi: 10.1038/s41416-023-02306-x

Key clinical point: According to an analysis of two large prospective US-based cohorts, the consumption of olive oil was not associated with an increased risk for breast cancer (BC) among women.

Major finding: Compared with women who never or rarely consumed olive oil, those with the highest consumption of olive oil (>1/2 tablespoon/day or >7 g/day) did not report an increased risk of developing BC (hazard ratio 1.01;  95% CI 0.93-1.09).

Study details: Findings are from an analysis of two large prospective cohorts of women who were free of cancer at baseline, the Nurses’ Health Study (n = 71,330) and Nurses’ Health Study II (n = 93,295), of whom 9638 women developed invasive BC after 3,744,068 person-years of follow-up.

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors declared no conflicts of interest.

Source: Romanos-Nanclares A et al. Consumption of olive oil and risk of breast cancer in U.S. women: Results from the Nurses' Health Studies. Br J Cancer. 2023 (Jun 13). Doi: 10.1038/s41416-023-02306-x

Key clinical point: According to an analysis of two large prospective US-based cohorts, the consumption of olive oil was not associated with an increased risk for breast cancer (BC) among women.

Major finding: Compared with women who never or rarely consumed olive oil, those with the highest consumption of olive oil (>1/2 tablespoon/day or >7 g/day) did not report an increased risk of developing BC (hazard ratio 1.01;  95% CI 0.93-1.09).

Study details: Findings are from an analysis of two large prospective cohorts of women who were free of cancer at baseline, the Nurses’ Health Study (n = 71,330) and Nurses’ Health Study II (n = 93,295), of whom 9638 women developed invasive BC after 3,744,068 person-years of follow-up.

Disclosures: This study was supported by the US National Institutes of Health and other sources. The authors declared no conflicts of interest.

Source: Romanos-Nanclares A et al. Consumption of olive oil and risk of breast cancer in U.S. women: Results from the Nurses' Health Studies. Br J Cancer. 2023 (Jun 13). Doi: 10.1038/s41416-023-02306-x

Key clinical point: Breast-conserving therapy (BCT) vs mastectomy resulted in higher improvement in survival without increasing the risk for locoregional recurrence (LRR) in patients with breast cancer (BC), regardless of their clinical nodal status.

Major finding: BCT vs mastectomy improved overall survival (hazard ratio [HR] 1.37; P < .001, and HR 1.46; P < .001, respectively) and BC-specific survival (HR 1.32; P < .001, and HR 1.44; P = .008, respectively) without increasing the risk for LRR (P = .14 and P = .70, respectively) in patients with clinical node-negative and node-positive BC.

Study details: Findings are from an analysis including 13,914 women with T1-3N0-3 BC (clinically node-negative BC n = 12,537 and clinically node-positive BC n = 1,377) from a prospectively maintained database, the majority of whom received systemic therapy.

Disclosures: This study did not declare the source of funding. The authors did not report any conflicts of interest.

Source: Vasilyeva E et al. Breast-conserving therapy is associated with improved survival without an increased risk of locoregional recurrence compared with mastectomy in both clinically node-positive and node-negative breast cancer patients. Ann Surg Oncol. 2023 (Jun 26). Doi: 10.1245/s10434-023-13784-x

Key clinical point: Breast-conserving therapy (BCT) vs mastectomy resulted in higher improvement in survival without increasing the risk for locoregional recurrence (LRR) in patients with breast cancer (BC), regardless of their clinical nodal status.

Major finding: BCT vs mastectomy improved overall survival (hazard ratio [HR] 1.37; P < .001, and HR 1.46; P < .001, respectively) and BC-specific survival (HR 1.32; P < .001, and HR 1.44; P = .008, respectively) without increasing the risk for LRR (P = .14 and P = .70, respectively) in patients with clinical node-negative and node-positive BC.

Study details: Findings are from an analysis including 13,914 women with T1-3N0-3 BC (clinically node-negative BC n = 12,537 and clinically node-positive BC n = 1,377) from a prospectively maintained database, the majority of whom received systemic therapy.

Disclosures: This study did not declare the source of funding. The authors did not report any conflicts of interest.

Source: Vasilyeva E et al. Breast-conserving therapy is associated with improved survival without an increased risk of locoregional recurrence compared with mastectomy in both clinically node-positive and node-negative breast cancer patients. Ann Surg Oncol. 2023 (Jun 26). Doi: 10.1245/s10434-023-13784-x

Key clinical point: Breast-conserving therapy (BCT) vs mastectomy resulted in higher improvement in survival without increasing the risk for locoregional recurrence (LRR) in patients with breast cancer (BC), regardless of their clinical nodal status.

Major finding: BCT vs mastectomy improved overall survival (hazard ratio [HR] 1.37; P < .001, and HR 1.46; P < .001, respectively) and BC-specific survival (HR 1.32; P < .001, and HR 1.44; P = .008, respectively) without increasing the risk for LRR (P = .14 and P = .70, respectively) in patients with clinical node-negative and node-positive BC.

Study details: Findings are from an analysis including 13,914 women with T1-3N0-3 BC (clinically node-negative BC n = 12,537 and clinically node-positive BC n = 1,377) from a prospectively maintained database, the majority of whom received systemic therapy.

Disclosures: This study did not declare the source of funding. The authors did not report any conflicts of interest.

Source: Vasilyeva E et al. Breast-conserving therapy is associated with improved survival without an increased risk of locoregional recurrence compared with mastectomy in both clinically node-positive and node-negative breast cancer patients. Ann Surg Oncol. 2023 (Jun 26). Doi: 10.1245/s10434-023-13784-x

Key clinical point: A neoadjuvant chemotherapy regimen with three cycles of fluorouracil, epirubicin, and cyclophosphamide followed by three cycles of docetaxel (FEC3‑D3) had comparable survival outcomes as four cycles of adriamycin and cyclophosphamide followed by four cycles of docetaxel (AC4‑D4) in patients with stage II/III breast cancer (BC).

Major finding: In the FEC3-D3 vs AC4-D4 treatment group, the pathological complete response rate was 12.4% vs 14.3%, respectively, and the 3-year disease-free survival rate was comparable (75.8% vs 75.6%). Grade 3/4 neutropenia was the most common adverse event in both groups (~20%).

Study details: Findings are from the phase 3, Neo-shorter study including 248 patients with stage II/III BC who were randomly assigned to receive FEC3-D3 or AC4-D4.

Disclosures: This study was supported by Sanofi-Aventis. Two authors declared serving as consultants, founders, or advisors; owning stocks in; or receiving research funding from various sources, including Sanofi. Other authors declared no conflicts of interest.

Source: Hwang I et al. Randomized phase III trial of a neoadjuvant regimen of four cycles of adriamycin plus cyclophosphamide followed by four cycles of docetaxel (AC4-D4) versus a shorter treatment of three cycles of FEC followed by three cycles of docetaxel (FEC3-D3) in node-positive breast cancer (Neo-shorter; NCT02001506). Breast Cancer Res Treat. 2023 (Jun 26). Doi: 10.1007/s10549-023-06971-7

Key clinical point: A neoadjuvant chemotherapy regimen with three cycles of fluorouracil, epirubicin, and cyclophosphamide followed by three cycles of docetaxel (FEC3‑D3) had comparable survival outcomes as four cycles of adriamycin and cyclophosphamide followed by four cycles of docetaxel (AC4‑D4) in patients with stage II/III breast cancer (BC).

Major finding: In the FEC3-D3 vs AC4-D4 treatment group, the pathological complete response rate was 12.4% vs 14.3%, respectively, and the 3-year disease-free survival rate was comparable (75.8% vs 75.6%). Grade 3/4 neutropenia was the most common adverse event in both groups (~20%).

Study details: Findings are from the phase 3, Neo-shorter study including 248 patients with stage II/III BC who were randomly assigned to receive FEC3-D3 or AC4-D4.

Disclosures: This study was supported by Sanofi-Aventis. Two authors declared serving as consultants, founders, or advisors; owning stocks in; or receiving research funding from various sources, including Sanofi. Other authors declared no conflicts of interest.

Source: Hwang I et al. Randomized phase III trial of a neoadjuvant regimen of four cycles of adriamycin plus cyclophosphamide followed by four cycles of docetaxel (AC4-D4) versus a shorter treatment of three cycles of FEC followed by three cycles of docetaxel (FEC3-D3) in node-positive breast cancer (Neo-shorter; NCT02001506). Breast Cancer Res Treat. 2023 (Jun 26). Doi: 10.1007/s10549-023-06971-7

Key clinical point: A neoadjuvant chemotherapy regimen with three cycles of fluorouracil, epirubicin, and cyclophosphamide followed by three cycles of docetaxel (FEC3‑D3) had comparable survival outcomes as four cycles of adriamycin and cyclophosphamide followed by four cycles of docetaxel (AC4‑D4) in patients with stage II/III breast cancer (BC).

Major finding: In the FEC3-D3 vs AC4-D4 treatment group, the pathological complete response rate was 12.4% vs 14.3%, respectively, and the 3-year disease-free survival rate was comparable (75.8% vs 75.6%). Grade 3/4 neutropenia was the most common adverse event in both groups (~20%).

Study details: Findings are from the phase 3, Neo-shorter study including 248 patients with stage II/III BC who were randomly assigned to receive FEC3-D3 or AC4-D4.

Disclosures: This study was supported by Sanofi-Aventis. Two authors declared serving as consultants, founders, or advisors; owning stocks in; or receiving research funding from various sources, including Sanofi. Other authors declared no conflicts of interest.

Source: Hwang I et al. Randomized phase III trial of a neoadjuvant regimen of four cycles of adriamycin plus cyclophosphamide followed by four cycles of docetaxel (AC4-D4) versus a shorter treatment of three cycles of FEC followed by three cycles of docetaxel (FEC3-D3) in node-positive breast cancer (Neo-shorter; NCT02001506). Breast Cancer Res Treat. 2023 (Jun 26). Doi: 10.1007/s10549-023-06971-7

Key clinical point: Rates of locoregional recurrence after surgery were different for different molecular subtypes of breast cancer (BC).

Major finding: Compared with patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-negative (ERBB2− aka HER2−) BC, those with HR−/ERBB2+ BC had approximately three times worse ipsilateral breast tumor recurrence (IBTR)-free survival (adjusted hazard ratio [aHR] 2.95;  95% CI 2.15-4.06), whereas patients with triple-negative BC had the worst regional recurrence-free survival (aHR 2.95;  95% CI 2.37-3.67) and contralateral BC-free survival (aHR 2.12;  95% CI 1.64-2.75). IBTR was lower in older patients with BC (P < .001).

Study details: Findings are from a retrospective cohort study including 16,462 women with BC who underwent surgery.

Disclosures: This study was funded by the Ministry of Health and Welfare, Republic of Korea. Some authors declared being members of a board of directors, stockholders of, or receiving grants from various sources.

Source: Cheun JH et al. Locoregional recurrence patterns in patients with different molecular subtypes of breast cancer. JAMA Surg. 2023 (Jun 21). Doi: 10.1001/jamasurg.2023.2150

Key clinical point: Rates of locoregional recurrence after surgery were different for different molecular subtypes of breast cancer (BC).

Major finding: Compared with patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-negative (ERBB2− aka HER2−) BC, those with HR−/ERBB2+ BC had approximately three times worse ipsilateral breast tumor recurrence (IBTR)-free survival (adjusted hazard ratio [aHR] 2.95;  95% CI 2.15-4.06), whereas patients with triple-negative BC had the worst regional recurrence-free survival (aHR 2.95;  95% CI 2.37-3.67) and contralateral BC-free survival (aHR 2.12;  95% CI 1.64-2.75). IBTR was lower in older patients with BC (P < .001).

Study details: Findings are from a retrospective cohort study including 16,462 women with BC who underwent surgery.

Disclosures: This study was funded by the Ministry of Health and Welfare, Republic of Korea. Some authors declared being members of a board of directors, stockholders of, or receiving grants from various sources.

Source: Cheun JH et al. Locoregional recurrence patterns in patients with different molecular subtypes of breast cancer. JAMA Surg. 2023 (Jun 21). Doi: 10.1001/jamasurg.2023.2150

Key clinical point: Rates of locoregional recurrence after surgery were different for different molecular subtypes of breast cancer (BC).

Major finding: Compared with patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-negative (ERBB2− aka HER2−) BC, those with HR−/ERBB2+ BC had approximately three times worse ipsilateral breast tumor recurrence (IBTR)-free survival (adjusted hazard ratio [aHR] 2.95;  95% CI 2.15-4.06), whereas patients with triple-negative BC had the worst regional recurrence-free survival (aHR 2.95;  95% CI 2.37-3.67) and contralateral BC-free survival (aHR 2.12;  95% CI 1.64-2.75). IBTR was lower in older patients with BC (P < .001).

Study details: Findings are from a retrospective cohort study including 16,462 women with BC who underwent surgery.

Disclosures: This study was funded by the Ministry of Health and Welfare, Republic of Korea. Some authors declared being members of a board of directors, stockholders of, or receiving grants from various sources.

Source: Cheun JH et al. Locoregional recurrence patterns in patients with different molecular subtypes of breast cancer. JAMA Surg. 2023 (Jun 21). Doi: 10.1001/jamasurg.2023.2150

Key clinical point: Pathologic regional lymph node stages I-III (pN1-3) and pathologic tumor size stage IV (pT4) were associated with worse long-term breast-cancer–specific survival (BCSS) outcomes in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC).

Major finding: In patients who were followed up for more than 60 months, increasing vs no nodal involvement (pN1-3 vs pN0; all hazard ratios [HR] >3; all P ≤ .001) and a tumor size of pT4 vs pT1 (HR 4.528; P = .007) were associated with poor BCSS outcomes.

Study details: This study used data from a registry to analyze 20,672 patients with HER2+ stage I-III BC who underwent surgery.

Disclosures: This study was supported by the Korean Breast Cancer Society. The authors declared no conflicts of interest.

Source: Kang YJ et al. Predictive biological factors for late survival in patients with HER2-positive breast cancer. Sci Rep. 2023;13:11008 (Jul 7). Doi: 10.1038/s41598-023-38200-y

Key clinical point: Pathologic regional lymph node stages I-III (pN1-3) and pathologic tumor size stage IV (pT4) were associated with worse long-term breast-cancer–specific survival (BCSS) outcomes in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC).

Major finding: In patients who were followed up for more than 60 months, increasing vs no nodal involvement (pN1-3 vs pN0; all hazard ratios [HR] >3; all P ≤ .001) and a tumor size of pT4 vs pT1 (HR 4.528; P = .007) were associated with poor BCSS outcomes.

Study details: This study used data from a registry to analyze 20,672 patients with HER2+ stage I-III BC who underwent surgery.

Disclosures: This study was supported by the Korean Breast Cancer Society. The authors declared no conflicts of interest.

Source: Kang YJ et al. Predictive biological factors for late survival in patients with HER2-positive breast cancer. Sci Rep. 2023;13:11008 (Jul 7). Doi: 10.1038/s41598-023-38200-y

Key clinical point: Pathologic regional lymph node stages I-III (pN1-3) and pathologic tumor size stage IV (pT4) were associated with worse long-term breast-cancer–specific survival (BCSS) outcomes in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC).

Major finding: In patients who were followed up for more than 60 months, increasing vs no nodal involvement (pN1-3 vs pN0; all hazard ratios [HR] >3; all P ≤ .001) and a tumor size of pT4 vs pT1 (HR 4.528; P = .007) were associated with poor BCSS outcomes.

Study details: This study used data from a registry to analyze 20,672 patients with HER2+ stage I-III BC who underwent surgery.

Disclosures: This study was supported by the Korean Breast Cancer Society. The authors declared no conflicts of interest.

Source: Kang YJ et al. Predictive biological factors for late survival in patients with HER2-positive breast cancer. Sci Rep. 2023;13:11008 (Jul 7). Doi: 10.1038/s41598-023-38200-y

Key clinical point:Although the cumulative incidence of myeloid neoplasms, such as myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML), was low in breast cancer (BC) survivors, the receipt of anthracycline-based adjuvant therapy was associated with a long-term risk for both AML and MDS.

Major finding: The 10-year cumulative incidences of both AML and MDS were very low (~0.2%) in the anthracycline group and <0.2% in the chemotherapy without anthracycline and no chemotherapy groups. However, the risk for AML (hazard ratio [HR] 9.531;  95% CI 4.156-21.861) and MDS (HR 2.559;  95% CI 1.600-4.095) was significantly higher in the anthracycline group vs no chemotherapy group.

Study details: Findings are from a retrospective cohort study including 153,565 patients with BC who underwent surgery and received adjuvant treatment with anthracyclines (n = 79,321), chemotherapy without anthracyclines (n = 15,475), or no chemotherapy (n = 46,657).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Lee JW et al. Therapy related myeloid neoplasm in early breast cancer patients treated with adjuvant chemotherapy. Eur J Cancer. 2023;191:112952 (Jun 22). Doi: 10.1016/j.ejca.2023.112952

Key clinical point:Although the cumulative incidence of myeloid neoplasms, such as myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML), was low in breast cancer (BC) survivors, the receipt of anthracycline-based adjuvant therapy was associated with a long-term risk for both AML and MDS.

Major finding: The 10-year cumulative incidences of both AML and MDS were very low (~0.2%) in the anthracycline group and <0.2% in the chemotherapy without anthracycline and no chemotherapy groups. However, the risk for AML (hazard ratio [HR] 9.531;  95% CI 4.156-21.861) and MDS (HR 2.559;  95% CI 1.600-4.095) was significantly higher in the anthracycline group vs no chemotherapy group.

Study details: Findings are from a retrospective cohort study including 153,565 patients with BC who underwent surgery and received adjuvant treatment with anthracyclines (n = 79,321), chemotherapy without anthracyclines (n = 15,475), or no chemotherapy (n = 46,657).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Lee JW et al. Therapy related myeloid neoplasm in early breast cancer patients treated with adjuvant chemotherapy. Eur J Cancer. 2023;191:112952 (Jun 22). Doi: 10.1016/j.ejca.2023.112952

Key clinical point:Although the cumulative incidence of myeloid neoplasms, such as myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML), was low in breast cancer (BC) survivors, the receipt of anthracycline-based adjuvant therapy was associated with a long-term risk for both AML and MDS.

Major finding: The 10-year cumulative incidences of both AML and MDS were very low (~0.2%) in the anthracycline group and <0.2% in the chemotherapy without anthracycline and no chemotherapy groups. However, the risk for AML (hazard ratio [HR] 9.531;  95% CI 4.156-21.861) and MDS (HR 2.559;  95% CI 1.600-4.095) was significantly higher in the anthracycline group vs no chemotherapy group.

Study details: Findings are from a retrospective cohort study including 153,565 patients with BC who underwent surgery and received adjuvant treatment with anthracyclines (n = 79,321), chemotherapy without anthracyclines (n = 15,475), or no chemotherapy (n = 46,657).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Lee JW et al. Therapy related myeloid neoplasm in early breast cancer patients treated with adjuvant chemotherapy. Eur J Cancer. 2023;191:112952 (Jun 22). Doi: 10.1016/j.ejca.2023.112952

Key clinical point: Patients with germline (g) BRCA1/2-associated primary breast cancer (BC), particularly those with gBRCA2 pathogenic mutations, faced a moderately increased risk of developing contralateral breast cancer (CBC) after receiving adjuvant radiotherapy.

Major finding: The risk for invasive and in situ CBC increased by 44% in patients with gBRCA1/2 mutations who did vs did not receive radiotherapy (adjusted hazard ratio [HR] 1.44;  95% CI 1.12-1.86), with the risk being even more prominent in gBRCA2 pathogenic variant carriers (adjusted HR 1.77;  95% CI 1.13-2.77).

Study details: Findings are from an analysis including 3602 patients with gBRCA1/2-associated primary BC from the prospective international BRCA1/2 Carrier Cohort Study, of whom 64% of patients received adjuvant radiotherapy.

Disclosures: This study did not receive any specific external funding. DG Evans reported ties with AstraZeneca and AmGen, K Kast declared ties with Roche Pharma AG, and J Simard declared holding patents related to BRCA1 and BRCA2.

Source: van Barele M et al. Contralateral breast cancer risk in irradiated breast cancer patients with a germline-BRCA1/2 pathogenic variant. J Natl Cancer Inst. 2023 (Jun 27). Doi: 10.1093/jnci/djad116

Key clinical point: Patients with germline (g) BRCA1/2-associated primary breast cancer (BC), particularly those with gBRCA2 pathogenic mutations, faced a moderately increased risk of developing contralateral breast cancer (CBC) after receiving adjuvant radiotherapy.

Major finding: The risk for invasive and in situ CBC increased by 44% in patients with gBRCA1/2 mutations who did vs did not receive radiotherapy (adjusted hazard ratio [HR] 1.44;  95% CI 1.12-1.86), with the risk being even more prominent in gBRCA2 pathogenic variant carriers (adjusted HR 1.77;  95% CI 1.13-2.77).

Study details: Findings are from an analysis including 3602 patients with gBRCA1/2-associated primary BC from the prospective international BRCA1/2 Carrier Cohort Study, of whom 64% of patients received adjuvant radiotherapy.

Disclosures: This study did not receive any specific external funding. DG Evans reported ties with AstraZeneca and AmGen, K Kast declared ties with Roche Pharma AG, and J Simard declared holding patents related to BRCA1 and BRCA2.

Source: van Barele M et al. Contralateral breast cancer risk in irradiated breast cancer patients with a germline-BRCA1/2 pathogenic variant. J Natl Cancer Inst. 2023 (Jun 27). Doi: 10.1093/jnci/djad116

Key clinical point: Patients with germline (g) BRCA1/2-associated primary breast cancer (BC), particularly those with gBRCA2 pathogenic mutations, faced a moderately increased risk of developing contralateral breast cancer (CBC) after receiving adjuvant radiotherapy.

Major finding: The risk for invasive and in situ CBC increased by 44% in patients with gBRCA1/2 mutations who did vs did not receive radiotherapy (adjusted hazard ratio [HR] 1.44;  95% CI 1.12-1.86), with the risk being even more prominent in gBRCA2 pathogenic variant carriers (adjusted HR 1.77;  95% CI 1.13-2.77).

Study details: Findings are from an analysis including 3602 patients with gBRCA1/2-associated primary BC from the prospective international BRCA1/2 Carrier Cohort Study, of whom 64% of patients received adjuvant radiotherapy.

Disclosures: This study did not receive any specific external funding. DG Evans reported ties with AstraZeneca and AmGen, K Kast declared ties with Roche Pharma AG, and J Simard declared holding patents related to BRCA1 and BRCA2.

Source: van Barele M et al. Contralateral breast cancer risk in irradiated breast cancer patients with a germline-BRCA1/2 pathogenic variant. J Natl Cancer Inst. 2023 (Jun 27). Doi: 10.1093/jnci/djad116

Key clinical point: Patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (ERBB2−, aka HER2-) breast cancer (BC) experienced very low locoregional recurrence (LRR) events and comparable invasive disease-free survival (iDFS) outcomes both with and without receiving regional nodal irradiation (RNI) after surgery.

Major finding: The cumulative incidence of LRR at 5 years was low among patients who underwent breast-conserving surgery and radiotherapy with RNI (0.85%), breast-conserving surgery and radiotherapy without RNI (0.55%), mastectomy followed by radiotherapy (0.11%), or mastectomy without radiotherapy (1.7%). Receiving RNI was not associated with better iDFS outcomes (P > .1 for both pre- and postmenopausal women).

Study details: Findings are from the secondary analysis of the SWOG S1007 trial including 4871 women with HR+/ERBB2− node-positive BC, of whom 2274 women received RNI.

Disclosures: This study was supported by the US National Institutes of Health (NIH) and other sources. Some authors declared serving as consultants or receiving grants and personal fees from various sources, including NIH.

Source: Jagsi R et al. Radiotherapy use and incidence of locoregional recurrence in patients with favorable-risk, node-positive breast cancer enrolled in the SWOG S1007 trial. JAMA Oncol. 2023 (Jul 6). Doi: 10.1001/jamaoncol.2023.1984

Key clinical point: Patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (ERBB2−, aka HER2-) breast cancer (BC) experienced very low locoregional recurrence (LRR) events and comparable invasive disease-free survival (iDFS) outcomes both with and without receiving regional nodal irradiation (RNI) after surgery.

Major finding: The cumulative incidence of LRR at 5 years was low among patients who underwent breast-conserving surgery and radiotherapy with RNI (0.85%), breast-conserving surgery and radiotherapy without RNI (0.55%), mastectomy followed by radiotherapy (0.11%), or mastectomy without radiotherapy (1.7%). Receiving RNI was not associated with better iDFS outcomes (P > .1 for both pre- and postmenopausal women).

Study details: Findings are from the secondary analysis of the SWOG S1007 trial including 4871 women with HR+/ERBB2− node-positive BC, of whom 2274 women received RNI.

Disclosures: This study was supported by the US National Institutes of Health (NIH) and other sources. Some authors declared serving as consultants or receiving grants and personal fees from various sources, including NIH.

Source: Jagsi R et al. Radiotherapy use and incidence of locoregional recurrence in patients with favorable-risk, node-positive breast cancer enrolled in the SWOG S1007 trial. JAMA Oncol. 2023 (Jul 6). Doi: 10.1001/jamaoncol.2023.1984

Key clinical point: Patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (ERBB2−, aka HER2-) breast cancer (BC) experienced very low locoregional recurrence (LRR) events and comparable invasive disease-free survival (iDFS) outcomes both with and without receiving regional nodal irradiation (RNI) after surgery.

Major finding: The cumulative incidence of LRR at 5 years was low among patients who underwent breast-conserving surgery and radiotherapy with RNI (0.85%), breast-conserving surgery and radiotherapy without RNI (0.55%), mastectomy followed by radiotherapy (0.11%), or mastectomy without radiotherapy (1.7%). Receiving RNI was not associated with better iDFS outcomes (P > .1 for both pre- and postmenopausal women).

Study details: Findings are from the secondary analysis of the SWOG S1007 trial including 4871 women with HR+/ERBB2− node-positive BC, of whom 2274 women received RNI.

Disclosures: This study was supported by the US National Institutes of Health (NIH) and other sources. Some authors declared serving as consultants or receiving grants and personal fees from various sources, including NIH.

Source: Jagsi R et al. Radiotherapy use and incidence of locoregional recurrence in patients with favorable-risk, node-positive breast cancer enrolled in the SWOG S1007 trial. JAMA Oncol. 2023 (Jul 6). Doi: 10.1001/jamaoncol.2023.1984

Higher rates of cervical cancer screening are associated with an increased risk of preterm delivery (PTD) in young nulliparous women aged 18-24 years, a large population-based study found.

For each additional recommended screening before childbirth, there was a direct increase in absolute PTD risk of 0.073 (95% confidence interval, 0.026-0.120), according to a study led by Rebecca A. Bromley-Dulfano, MS, an MD candidate at Stanford (Calif.) University and a PhD candidate in health policy at Harvard University, Cambridge, Mass.

courtesy Ms. Bromley-Dulfano

There was no significant change in very preterm delivery (VPTD) risk, but mothers with hypertension or diabetes were at higher PTD risk.

Women in this younger age group are more prone to PTD. According to the study’s estimate, an additional 73 PTDs per 100,000 women could be expected for every 1 additional recommended screening before childbirth. For the year 2018, that translated to an estimated 1,348 PTDs that could have been averted, with reduced screening requirements (3% relative reduction).

“If you screen someone for cervical cancer and find a cervical lesion, the possible next steps can include a biopsy and an excisional procedure to remove the lesion,” Ms. Bromley-Dulfano explained, “and these procedures which remove a small (mostly diseased) part of the cervix have been shown to slightly increase the risk of PTD. Particularly in young individuals with a cervix who are known to have high rates of lesion regression and who have more potential childbearing years ahead of them, it is important to weigh the oncological benefits with the adverse birth outcome risks.” 

Young women are more likely to have false-positive results on Papanicolaou tests and lesion regression within 2 years but may undergo unnecessary treatment, the authors noted.

Cervical excision procedures have previously been associated in clinical trials with an increase in PTB risk.

In their 2017 decision model in a fictive cohort, for example, Kamphuis and colleagues found the most intensive screening program was associated with an increase in maternal life years of 9%, a decrease in cervical cancer incidence of 67%, and a decrease in cervical cancer deaths of 75%. But those gains came at the cost of 250% more preterm births, compared with the least intensive program.

“These results can be used in future simulation models integrating oncological trade-offs to help ascertain optimal screening strategies,” the researchers wrote.

While the optimal screening strategy must trade off the oncologic benefits of cancer detection against the neonatal harms of overtreatment, the ideal age of cervical cancer screening onset and frequency remain uncertain, the authors noted. Recent American Cancer Society guidelines recommending less frequent screening for some diverge from those of other societies.

“The first and foremost priority is for gynecologists to continue to have individualized conversations with patients about all of the benefits and risks of procedures that patients undergo and to understand the benefits and risks influencing screening guidelines,” Ms. Bromley-Dulfano said.
 

Cross-sectional study

The study used data from the Centers for Disease Control and Prevention’s National Center for Health Statistics to analyze associations between cervical cancer screening guidelines and birth outcomes women who had a singleton nulliparous birth from 19916 to 2018. Gestational age and maternal characteristics were drawn from birth certificates.

The mean age of the 11,333,151 multiracial cohort of women was 20.9 years, and 6.8% had hypertension or diabetes. The mean number of guideline-recommended screenings by time of childbirth was 2.4. Overall, PTD and very PTD occurred in 1,140,490 individuals (10.1%) and 333,040 (2.9%) of births, respectively.

Those with hypertension or diabetes had a somewhat higher PTD risk: 0.26% (95% CI, 0.11-0.4) versus 0.06% (95% CI, 0.01-0.10; Wald test, P < .001).

courtesy Northwell Health

Offering an outsider’s perspective on the analysis, ob.gyn. Fidel A. Valea, MD, director of gynecologic oncology at the Northwell Health Cancer Institute in New Hyde Park, N.Y., urged caution in drawing conclusions from large population analyses such as this.

“This study had over 11 million data points. Often these large numbers will show statistical differences that are not clinically significant,” he said in an interview. He noted that while small studies have shown a possible impact of frequent Pap tests on cervical function, “this is not 100% proven. Research from Texas showed that screening made a difference only in cases of dysplasia.”

Dr. Valea also noted that screening guidelines have already changed over the lengthy time span of the study and do reflect the concerns of the study authors.

“We know that the HPV virus is cleared more readily by young women than older women and so we have made adjustments and test them less frequently and we test them less early.” He added that conservative options are recommended even in the case of dysplasia.

In defense of the Pap smear test, he added: “It has virtually wiped out cervical cancer in the U.S., bringing it from No. 1 to No. 13.” While broadening HPV vaccination programs may impact guidelines in the future, “vaccination is still in its infancy. We have to wait until women have lived long to enough to see an impact.”

As to why this age group is more vulnerable to PTD, Dr. Valea said, “It’s likely multifactorial, with lifestyle and other factors involved.” Although based on U.S. data, the authors said their results may be useful for other public health entities, particularly in countries where cervical cancer is considerably more prevalent.

This work received no specific funding. The authors and Dr. Valea disclosed no competing interests.

Higher rates of cervical cancer screening are associated with an increased risk of preterm delivery (PTD) in young nulliparous women aged 18-24 years, a large population-based study found.

For each additional recommended screening before childbirth, there was a direct increase in absolute PTD risk of 0.073 (95% confidence interval, 0.026-0.120), according to a study led by Rebecca A. Bromley-Dulfano, MS, an MD candidate at Stanford (Calif.) University and a PhD candidate in health policy at Harvard University, Cambridge, Mass.

courtesy Ms. Bromley-Dulfano

There was no significant change in very preterm delivery (VPTD) risk, but mothers with hypertension or diabetes were at higher PTD risk.

Women in this younger age group are more prone to PTD. According to the study’s estimate, an additional 73 PTDs per 100,000 women could be expected for every 1 additional recommended screening before childbirth. For the year 2018, that translated to an estimated 1,348 PTDs that could have been averted, with reduced screening requirements (3% relative reduction).

“If you screen someone for cervical cancer and find a cervical lesion, the possible next steps can include a biopsy and an excisional procedure to remove the lesion,” Ms. Bromley-Dulfano explained, “and these procedures which remove a small (mostly diseased) part of the cervix have been shown to slightly increase the risk of PTD. Particularly in young individuals with a cervix who are known to have high rates of lesion regression and who have more potential childbearing years ahead of them, it is important to weigh the oncological benefits with the adverse birth outcome risks.” 

Young women are more likely to have false-positive results on Papanicolaou tests and lesion regression within 2 years but may undergo unnecessary treatment, the authors noted.

Cervical excision procedures have previously been associated in clinical trials with an increase in PTB risk.

In their 2017 decision model in a fictive cohort, for example, Kamphuis and colleagues found the most intensive screening program was associated with an increase in maternal life years of 9%, a decrease in cervical cancer incidence of 67%, and a decrease in cervical cancer deaths of 75%. But those gains came at the cost of 250% more preterm births, compared with the least intensive program.

“These results can be used in future simulation models integrating oncological trade-offs to help ascertain optimal screening strategies,” the researchers wrote.

While the optimal screening strategy must trade off the oncologic benefits of cancer detection against the neonatal harms of overtreatment, the ideal age of cervical cancer screening onset and frequency remain uncertain, the authors noted. Recent American Cancer Society guidelines recommending less frequent screening for some diverge from those of other societies.

“The first and foremost priority is for gynecologists to continue to have individualized conversations with patients about all of the benefits and risks of procedures that patients undergo and to understand the benefits and risks influencing screening guidelines,” Ms. Bromley-Dulfano said.
 

Cross-sectional study

The study used data from the Centers for Disease Control and Prevention’s National Center for Health Statistics to analyze associations between cervical cancer screening guidelines and birth outcomes women who had a singleton nulliparous birth from 19916 to 2018. Gestational age and maternal characteristics were drawn from birth certificates.

The mean age of the 11,333,151 multiracial cohort of women was 20.9 years, and 6.8% had hypertension or diabetes. The mean number of guideline-recommended screenings by time of childbirth was 2.4. Overall, PTD and very PTD occurred in 1,140,490 individuals (10.1%) and 333,040 (2.9%) of births, respectively.

Those with hypertension or diabetes had a somewhat higher PTD risk: 0.26% (95% CI, 0.11-0.4) versus 0.06% (95% CI, 0.01-0.10; Wald test, P < .001).

courtesy Northwell Health

Offering an outsider’s perspective on the analysis, ob.gyn. Fidel A. Valea, MD, director of gynecologic oncology at the Northwell Health Cancer Institute in New Hyde Park, N.Y., urged caution in drawing conclusions from large population analyses such as this.

“This study had over 11 million data points. Often these large numbers will show statistical differences that are not clinically significant,” he said in an interview. He noted that while small studies have shown a possible impact of frequent Pap tests on cervical function, “this is not 100% proven. Research from Texas showed that screening made a difference only in cases of dysplasia.”

Dr. Valea also noted that screening guidelines have already changed over the lengthy time span of the study and do reflect the concerns of the study authors.

“We know that the HPV virus is cleared more readily by young women than older women and so we have made adjustments and test them less frequently and we test them less early.” He added that conservative options are recommended even in the case of dysplasia.

In defense of the Pap smear test, he added: “It has virtually wiped out cervical cancer in the U.S., bringing it from No. 1 to No. 13.” While broadening HPV vaccination programs may impact guidelines in the future, “vaccination is still in its infancy. We have to wait until women have lived long to enough to see an impact.”

As to why this age group is more vulnerable to PTD, Dr. Valea said, “It’s likely multifactorial, with lifestyle and other factors involved.” Although based on U.S. data, the authors said their results may be useful for other public health entities, particularly in countries where cervical cancer is considerably more prevalent.

This work received no specific funding. The authors and Dr. Valea disclosed no competing interests.

Higher rates of cervical cancer screening are associated with an increased risk of preterm delivery (PTD) in young nulliparous women aged 18-24 years, a large population-based study found.

For each additional recommended screening before childbirth, there was a direct increase in absolute PTD risk of 0.073 (95% confidence interval, 0.026-0.120), according to a study led by Rebecca A. Bromley-Dulfano, MS, an MD candidate at Stanford (Calif.) University and a PhD candidate in health policy at Harvard University, Cambridge, Mass.

courtesy Ms. Bromley-Dulfano

There was no significant change in very preterm delivery (VPTD) risk, but mothers with hypertension or diabetes were at higher PTD risk.

Women in this younger age group are more prone to PTD. According to the study’s estimate, an additional 73 PTDs per 100,000 women could be expected for every 1 additional recommended screening before childbirth. For the year 2018, that translated to an estimated 1,348 PTDs that could have been averted, with reduced screening requirements (3% relative reduction).

“If you screen someone for cervical cancer and find a cervical lesion, the possible next steps can include a biopsy and an excisional procedure to remove the lesion,” Ms. Bromley-Dulfano explained, “and these procedures which remove a small (mostly diseased) part of the cervix have been shown to slightly increase the risk of PTD. Particularly in young individuals with a cervix who are known to have high rates of lesion regression and who have more potential childbearing years ahead of them, it is important to weigh the oncological benefits with the adverse birth outcome risks.” 

Young women are more likely to have false-positive results on Papanicolaou tests and lesion regression within 2 years but may undergo unnecessary treatment, the authors noted.

Cervical excision procedures have previously been associated in clinical trials with an increase in PTB risk.

In their 2017 decision model in a fictive cohort, for example, Kamphuis and colleagues found the most intensive screening program was associated with an increase in maternal life years of 9%, a decrease in cervical cancer incidence of 67%, and a decrease in cervical cancer deaths of 75%. But those gains came at the cost of 250% more preterm births, compared with the least intensive program.

“These results can be used in future simulation models integrating oncological trade-offs to help ascertain optimal screening strategies,” the researchers wrote.

While the optimal screening strategy must trade off the oncologic benefits of cancer detection against the neonatal harms of overtreatment, the ideal age of cervical cancer screening onset and frequency remain uncertain, the authors noted. Recent American Cancer Society guidelines recommending less frequent screening for some diverge from those of other societies.

“The first and foremost priority is for gynecologists to continue to have individualized conversations with patients about all of the benefits and risks of procedures that patients undergo and to understand the benefits and risks influencing screening guidelines,” Ms. Bromley-Dulfano said.
 

Cross-sectional study

The study used data from the Centers for Disease Control and Prevention’s National Center for Health Statistics to analyze associations between cervical cancer screening guidelines and birth outcomes women who had a singleton nulliparous birth from 19916 to 2018. Gestational age and maternal characteristics were drawn from birth certificates.

The mean age of the 11,333,151 multiracial cohort of women was 20.9 years, and 6.8% had hypertension or diabetes. The mean number of guideline-recommended screenings by time of childbirth was 2.4. Overall, PTD and very PTD occurred in 1,140,490 individuals (10.1%) and 333,040 (2.9%) of births, respectively.

Those with hypertension or diabetes had a somewhat higher PTD risk: 0.26% (95% CI, 0.11-0.4) versus 0.06% (95% CI, 0.01-0.10; Wald test, P < .001).

courtesy Northwell Health

Offering an outsider’s perspective on the analysis, ob.gyn. Fidel A. Valea, MD, director of gynecologic oncology at the Northwell Health Cancer Institute in New Hyde Park, N.Y., urged caution in drawing conclusions from large population analyses such as this.

“This study had over 11 million data points. Often these large numbers will show statistical differences that are not clinically significant,” he said in an interview. He noted that while small studies have shown a possible impact of frequent Pap tests on cervical function, “this is not 100% proven. Research from Texas showed that screening made a difference only in cases of dysplasia.”

Dr. Valea also noted that screening guidelines have already changed over the lengthy time span of the study and do reflect the concerns of the study authors.

“We know that the HPV virus is cleared more readily by young women than older women and so we have made adjustments and test them less frequently and we test them less early.” He added that conservative options are recommended even in the case of dysplasia.

In defense of the Pap smear test, he added: “It has virtually wiped out cervical cancer in the U.S., bringing it from No. 1 to No. 13.” While broadening HPV vaccination programs may impact guidelines in the future, “vaccination is still in its infancy. We have to wait until women have lived long to enough to see an impact.”

As to why this age group is more vulnerable to PTD, Dr. Valea said, “It’s likely multifactorial, with lifestyle and other factors involved.” Although based on U.S. data, the authors said their results may be useful for other public health entities, particularly in countries where cervical cancer is considerably more prevalent.

This work received no specific funding. The authors and Dr. Valea disclosed no competing interests.

Twice-weekly subcutaneous ketamine injections are safe and highly effective for treatment-resistant depression (TRD), results of a randomized controlled phase 3 trial show.
 

University of New South Wales

“In this severely treatment-resistant population, of which 24% had failed to respond to treatment with electroconvulsive therapy, adequately dosed racemic ketamine produced benefits that were large, being both clinically and statistically superior to midazolam,” report the researchers, led by Colleen Loo, MD, MBBS, with Black Dog Institute, University of New South Wales, Sydney.

The study was published online in the British Journal of Psychiatry.


 

Individualized dosing

“Previously, most studies of racemic ketamine [administered] it by intravenous infusion over half an hour to several hours, which is a much more medically complex and expensive procedure,” Dr. Loo said in an interview.

The fact that subcutaneously administered ketamine was “highly effective” given by this practical and feasible route is a “major contribution to the field,” said Dr. Loo.

The Ketamine for Adult Depression trial assessed the acute efficacy and safety of a 4-week course of twice-weekly subcutaneous injections of racemic ketamine or midazolam (active control) in 174 adults with TRD.

Initially, the trial tested a fixed dose of 0.5 mg/kg ketamine vs. 0.025 mg/kg midazolam (cohort 1; 68 patients). Dosing was subsequently revised, after the data safety monitoring board recommended flexible-dose ketamine (0.5-0.9 mg/kg) or midazolam (0.025-0.045 mg/kg) with response-guided dosing increments (cohort 2; 106 patients).

The primary outcome was remission defined as Montgomery-Åsberg Rating Scale for Depression (MADRS) score ≤ 10 at week 4.

On this outcome, in the fixed-dose cohort, there was no statistically significant difference in remission rates between ketamine and midazolam (6.3% and 8.8%; odds ratio, 1.34; 95% CI, 0.22-8.21; P = .76).

However, there was a significant difference in remission in the flexible-dose cohort, with remission rates 19.6% for ketamine vs. just 2% for midazolam (OR, 12.11; 95% CI, 2.12-69.17; P = .005).

“The study showed that individualized dose adjustment, based on clinical response, was very important in optimizing the benefit of ketamine,” said Dr. Loo.

“It meant that one, you are more likely to respond as you receive a higher dose if needed, and two, you don’t receive a higher dose than needed, given that side effects are also dose-related,” she said.

Results also favored flexible-dose ketamine over midazolam for the secondary outcomes of response (≥ 50% reduction in MADRS: 29% vs. 4%; P = .001) and remission defined by a less rigid definition (MADRS ≤ 12: 22% vs. 4%; P = .007).

The results also confirm that the antidepressant effects of ketamine are not sustained when treatment stops.

“The study included careful follow-up for 4 weeks after the end of treatment. This is an important contribution to the literature, as it shows that ongoing treatment beyond the 4 weeks will be necessary for most people to maintain the benefits of ketamine treatment if you respond to the treatment. This study provided clear evidence of this, for racemic ketamine,” said Dr. Loo.

Overall, ketamine was well-tolerated, with the well-established acute effects of ketamine observed in both cohorts. The acute effects resolved or returned to pretreatment levels within the 2-hour observation period. No one required medical intervention, and there was no evidence of cognitive impairment.
 

Rigorous research, compelling data

Reached for comment, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said the data are “compelling with respect to efficacy and safety of subcutaneous ketamine in adults with major depression.”

Dr. McIntyre said the data are “highly relevant” for several reasons. “First, it is the most rigorous study conducted to date with subcutaneous administration of ketamine for adults living with treatment-resistant depression.”

Second, it “demonstrates the efficacy and safety of this route of delivery, which until now has not been studied with this level of rigor and which is a more scalable and accessible approach to administer ketamine to suitable candidates,” Dr. McIntyre said.

The study was funded by a competitive research grant from the Australian National Health and Medical Research Council. Dr. Loo has disclosed relationships with Douglas Pharmaceuticals and Janssen Cilag and is the medical director of neurostimulation and interventional psychiatry at Ramsay Health Care. Dr. McIntyre has received speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, and Atai Life Sciences. Dr. McIntyre is a CEO of Braxia Scientific Corp.

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

Twice-weekly subcutaneous ketamine injections are safe and highly effective for treatment-resistant depression (TRD), results of a randomized controlled phase 3 trial show.
 

University of New South Wales

“In this severely treatment-resistant population, of which 24% had failed to respond to treatment with electroconvulsive therapy, adequately dosed racemic ketamine produced benefits that were large, being both clinically and statistically superior to midazolam,” report the researchers, led by Colleen Loo, MD, MBBS, with Black Dog Institute, University of New South Wales, Sydney.

The study was published online in the British Journal of Psychiatry.


 

Individualized dosing

“Previously, most studies of racemic ketamine [administered] it by intravenous infusion over half an hour to several hours, which is a much more medically complex and expensive procedure,” Dr. Loo said in an interview.

The fact that subcutaneously administered ketamine was “highly effective” given by this practical and feasible route is a “major contribution to the field,” said Dr. Loo.

The Ketamine for Adult Depression trial assessed the acute efficacy and safety of a 4-week course of twice-weekly subcutaneous injections of racemic ketamine or midazolam (active control) in 174 adults with TRD.

Initially, the trial tested a fixed dose of 0.5 mg/kg ketamine vs. 0.025 mg/kg midazolam (cohort 1; 68 patients). Dosing was subsequently revised, after the data safety monitoring board recommended flexible-dose ketamine (0.5-0.9 mg/kg) or midazolam (0.025-0.045 mg/kg) with response-guided dosing increments (cohort 2; 106 patients).

The primary outcome was remission defined as Montgomery-Åsberg Rating Scale for Depression (MADRS) score ≤ 10 at week 4.

On this outcome, in the fixed-dose cohort, there was no statistically significant difference in remission rates between ketamine and midazolam (6.3% and 8.8%; odds ratio, 1.34; 95% CI, 0.22-8.21; P = .76).

However, there was a significant difference in remission in the flexible-dose cohort, with remission rates 19.6% for ketamine vs. just 2% for midazolam (OR, 12.11; 95% CI, 2.12-69.17; P = .005).

“The study showed that individualized dose adjustment, based on clinical response, was very important in optimizing the benefit of ketamine,” said Dr. Loo.

“It meant that one, you are more likely to respond as you receive a higher dose if needed, and two, you don’t receive a higher dose than needed, given that side effects are also dose-related,” she said.

Results also favored flexible-dose ketamine over midazolam for the secondary outcomes of response (≥ 50% reduction in MADRS: 29% vs. 4%; P = .001) and remission defined by a less rigid definition (MADRS ≤ 12: 22% vs. 4%; P = .007).

The results also confirm that the antidepressant effects of ketamine are not sustained when treatment stops.

“The study included careful follow-up for 4 weeks after the end of treatment. This is an important contribution to the literature, as it shows that ongoing treatment beyond the 4 weeks will be necessary for most people to maintain the benefits of ketamine treatment if you respond to the treatment. This study provided clear evidence of this, for racemic ketamine,” said Dr. Loo.

Overall, ketamine was well-tolerated, with the well-established acute effects of ketamine observed in both cohorts. The acute effects resolved or returned to pretreatment levels within the 2-hour observation period. No one required medical intervention, and there was no evidence of cognitive impairment.
 

Rigorous research, compelling data

Reached for comment, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said the data are “compelling with respect to efficacy and safety of subcutaneous ketamine in adults with major depression.”

Dr. McIntyre said the data are “highly relevant” for several reasons. “First, it is the most rigorous study conducted to date with subcutaneous administration of ketamine for adults living with treatment-resistant depression.”

Second, it “demonstrates the efficacy and safety of this route of delivery, which until now has not been studied with this level of rigor and which is a more scalable and accessible approach to administer ketamine to suitable candidates,” Dr. McIntyre said.

The study was funded by a competitive research grant from the Australian National Health and Medical Research Council. Dr. Loo has disclosed relationships with Douglas Pharmaceuticals and Janssen Cilag and is the medical director of neurostimulation and interventional psychiatry at Ramsay Health Care. Dr. McIntyre has received speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, and Atai Life Sciences. Dr. McIntyre is a CEO of Braxia Scientific Corp.

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

Twice-weekly subcutaneous ketamine injections are safe and highly effective for treatment-resistant depression (TRD), results of a randomized controlled phase 3 trial show.
 

University of New South Wales

“In this severely treatment-resistant population, of which 24% had failed to respond to treatment with electroconvulsive therapy, adequately dosed racemic ketamine produced benefits that were large, being both clinically and statistically superior to midazolam,” report the researchers, led by Colleen Loo, MD, MBBS, with Black Dog Institute, University of New South Wales, Sydney.

The study was published online in the British Journal of Psychiatry.


 

Individualized dosing

“Previously, most studies of racemic ketamine [administered] it by intravenous infusion over half an hour to several hours, which is a much more medically complex and expensive procedure,” Dr. Loo said in an interview.

The fact that subcutaneously administered ketamine was “highly effective” given by this practical and feasible route is a “major contribution to the field,” said Dr. Loo.

The Ketamine for Adult Depression trial assessed the acute efficacy and safety of a 4-week course of twice-weekly subcutaneous injections of racemic ketamine or midazolam (active control) in 174 adults with TRD.

Initially, the trial tested a fixed dose of 0.5 mg/kg ketamine vs. 0.025 mg/kg midazolam (cohort 1; 68 patients). Dosing was subsequently revised, after the data safety monitoring board recommended flexible-dose ketamine (0.5-0.9 mg/kg) or midazolam (0.025-0.045 mg/kg) with response-guided dosing increments (cohort 2; 106 patients).

The primary outcome was remission defined as Montgomery-Åsberg Rating Scale for Depression (MADRS) score ≤ 10 at week 4.

On this outcome, in the fixed-dose cohort, there was no statistically significant difference in remission rates between ketamine and midazolam (6.3% and 8.8%; odds ratio, 1.34; 95% CI, 0.22-8.21; P = .76).

However, there was a significant difference in remission in the flexible-dose cohort, with remission rates 19.6% for ketamine vs. just 2% for midazolam (OR, 12.11; 95% CI, 2.12-69.17; P = .005).

“The study showed that individualized dose adjustment, based on clinical response, was very important in optimizing the benefit of ketamine,” said Dr. Loo.

“It meant that one, you are more likely to respond as you receive a higher dose if needed, and two, you don’t receive a higher dose than needed, given that side effects are also dose-related,” she said.

Results also favored flexible-dose ketamine over midazolam for the secondary outcomes of response (≥ 50% reduction in MADRS: 29% vs. 4%; P = .001) and remission defined by a less rigid definition (MADRS ≤ 12: 22% vs. 4%; P = .007).

The results also confirm that the antidepressant effects of ketamine are not sustained when treatment stops.

“The study included careful follow-up for 4 weeks after the end of treatment. This is an important contribution to the literature, as it shows that ongoing treatment beyond the 4 weeks will be necessary for most people to maintain the benefits of ketamine treatment if you respond to the treatment. This study provided clear evidence of this, for racemic ketamine,” said Dr. Loo.

Overall, ketamine was well-tolerated, with the well-established acute effects of ketamine observed in both cohorts. The acute effects resolved or returned to pretreatment levels within the 2-hour observation period. No one required medical intervention, and there was no evidence of cognitive impairment.
 

Rigorous research, compelling data

Reached for comment, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said the data are “compelling with respect to efficacy and safety of subcutaneous ketamine in adults with major depression.”

Dr. McIntyre said the data are “highly relevant” for several reasons. “First, it is the most rigorous study conducted to date with subcutaneous administration of ketamine for adults living with treatment-resistant depression.”

Second, it “demonstrates the efficacy and safety of this route of delivery, which until now has not been studied with this level of rigor and which is a more scalable and accessible approach to administer ketamine to suitable candidates,” Dr. McIntyre said.

The study was funded by a competitive research grant from the Australian National Health and Medical Research Council. Dr. Loo has disclosed relationships with Douglas Pharmaceuticals and Janssen Cilag and is the medical director of neurostimulation and interventional psychiatry at Ramsay Health Care. Dr. McIntyre has received speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, and Atai Life Sciences. Dr. McIntyre is a CEO of Braxia Scientific Corp.

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