Breast Cancer

Key clinical point: In patients with pT1aN0M0, human epidermal growth factor receptor 2 positive (HER2+) invasive breast cancer adding systemic therapy after surgical excision had clinical outcomes similar to local therapy alone.

Major finding: Overall survival was similar in all patients with pT1aN0M0 HER2-positive breast cancer who received local therapy+systemic therapy or only local therapy (P = .206), including the matched cohort of patients with hormone receptor positive (P = .107) and negative (P = .369) breast cancer.

Study details: This retrospective cohort study included 8948 patients with HER2+, pT1aN0M0 breast cancer, of which 4026 patients received local therapy only and 4922 patients received local therapy+adjuvant chemotherapy/HER2 therapy.

Disclosures: This study did not report any source of funding. CW Towe declared serving as consultant, providing expert testimony, and receiving research funding from several sources.

Source: Cao L et al. A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+ breast cancer: A National Cancer Database analysis. Cancer. 2022 (Apr 1). Doi: 10.1002/cncr.34200

Key clinical point: In patients with pT1aN0M0, human epidermal growth factor receptor 2 positive (HER2+) invasive breast cancer adding systemic therapy after surgical excision had clinical outcomes similar to local therapy alone.

Major finding: Overall survival was similar in all patients with pT1aN0M0 HER2-positive breast cancer who received local therapy+systemic therapy or only local therapy (P = .206), including the matched cohort of patients with hormone receptor positive (P = .107) and negative (P = .369) breast cancer.

Study details: This retrospective cohort study included 8948 patients with HER2+, pT1aN0M0 breast cancer, of which 4026 patients received local therapy only and 4922 patients received local therapy+adjuvant chemotherapy/HER2 therapy.

Disclosures: This study did not report any source of funding. CW Towe declared serving as consultant, providing expert testimony, and receiving research funding from several sources.

Source: Cao L et al. A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+ breast cancer: A National Cancer Database analysis. Cancer. 2022 (Apr 1). Doi: 10.1002/cncr.34200

Key clinical point: In patients with pT1aN0M0, human epidermal growth factor receptor 2 positive (HER2+) invasive breast cancer adding systemic therapy after surgical excision had clinical outcomes similar to local therapy alone.

Major finding: Overall survival was similar in all patients with pT1aN0M0 HER2-positive breast cancer who received local therapy+systemic therapy or only local therapy (P = .206), including the matched cohort of patients with hormone receptor positive (P = .107) and negative (P = .369) breast cancer.

Study details: This retrospective cohort study included 8948 patients with HER2+, pT1aN0M0 breast cancer, of which 4026 patients received local therapy only and 4922 patients received local therapy+adjuvant chemotherapy/HER2 therapy.

Disclosures: This study did not report any source of funding. CW Towe declared serving as consultant, providing expert testimony, and receiving research funding from several sources.

Source: Cao L et al. A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+ breast cancer: A National Cancer Database analysis. Cancer. 2022 (Apr 1). Doi: 10.1002/cncr.34200

Key clinical point: Imaging can be dependably used for estimating the size of clinical T1 tumors to plan lumpectomy; however, overestimation by preoperative imaging size (PIS) should be considered for larger tumors.

Major finding: Significant correlation was observed between PIS and postoperative pathology size (PPS), highest when estimated with ultrasound (correlation coefficient [r] 0.628) followed by mammography (r 0.571; both P < .001). Although ultrasound underestimated T1 (mean difference between PIS and PPS [MD] −3.47 mm; 95% CI −4.02 to −2.91 mm) and T2 (MD −2.20 mm; 95% CI −3.39 to −1.02 mm) tumors, mammogram underestimated T1 tumors (MD −2.91; 95% CI −3.51 to −2.32) and overestimated T2 tumors (MD 0.90; 95% CI −0.44 to 2.24), all within the range of concordance.

Study details: This study identified 1512 tumors in 1502 patients with invasive breast cancer who underwent their first surgery.

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

Source: Kapur H et al. Accuracy of preoperative imaging estimates: Opportunities to de-escalate surgery for early invasive breast cancer. Am J Surg. 2022 (Mar 30). Doi:  10.1016/j.amjsurg.2022.03.053

Key clinical point: Imaging can be dependably used for estimating the size of clinical T1 tumors to plan lumpectomy; however, overestimation by preoperative imaging size (PIS) should be considered for larger tumors.

Major finding: Significant correlation was observed between PIS and postoperative pathology size (PPS), highest when estimated with ultrasound (correlation coefficient [r] 0.628) followed by mammography (r 0.571; both P < .001). Although ultrasound underestimated T1 (mean difference between PIS and PPS [MD] −3.47 mm; 95% CI −4.02 to −2.91 mm) and T2 (MD −2.20 mm; 95% CI −3.39 to −1.02 mm) tumors, mammogram underestimated T1 tumors (MD −2.91; 95% CI −3.51 to −2.32) and overestimated T2 tumors (MD 0.90; 95% CI −0.44 to 2.24), all within the range of concordance.

Study details: This study identified 1512 tumors in 1502 patients with invasive breast cancer who underwent their first surgery.

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

Source: Kapur H et al. Accuracy of preoperative imaging estimates: Opportunities to de-escalate surgery for early invasive breast cancer. Am J Surg. 2022 (Mar 30). Doi:  10.1016/j.amjsurg.2022.03.053

Key clinical point: Imaging can be dependably used for estimating the size of clinical T1 tumors to plan lumpectomy; however, overestimation by preoperative imaging size (PIS) should be considered for larger tumors.

Major finding: Significant correlation was observed between PIS and postoperative pathology size (PPS), highest when estimated with ultrasound (correlation coefficient [r] 0.628) followed by mammography (r 0.571; both P < .001). Although ultrasound underestimated T1 (mean difference between PIS and PPS [MD] −3.47 mm; 95% CI −4.02 to −2.91 mm) and T2 (MD −2.20 mm; 95% CI −3.39 to −1.02 mm) tumors, mammogram underestimated T1 tumors (MD −2.91; 95% CI −3.51 to −2.32) and overestimated T2 tumors (MD 0.90; 95% CI −0.44 to 2.24), all within the range of concordance.

Study details: This study identified 1512 tumors in 1502 patients with invasive breast cancer who underwent their first surgery.

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

Source: Kapur H et al. Accuracy of preoperative imaging estimates: Opportunities to de-escalate surgery for early invasive breast cancer. Am J Surg. 2022 (Mar 30). Doi:  10.1016/j.amjsurg.2022.03.053

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.