Key clinical point: Some relatives of women with early-onset breast cancer (BC) may have an increased risk of developing discordant early-onset cancers (other than breast cancers).

Major finding: Among relatives of women with early-onset BC, offspring had a higher risk for any discordant early-onset cancer (standardized incidence ratio [SIR] 1.27; 95% CI 1.03-1.55), siblings' children had an increased risk for early-onset testicular cancer (SIR 1.74; 95% CI 1.07-2.69) and ovarian cancer (SIR 2.69; 95% CI 1.08-5.53), and siblings had an increased risk for early-onset pancreatic cancer (SIR 7.61; 95% CI 1.57-22.23).

Study details: Findings are from an analysis of a population-based cohort including 54,753 relatives from 5562 families of females diagnosed with early-onset BC.

Disclosures: This study was funded by the Cancer Foundation Finland and Academy of Finland. The authors declared no conflicts of interest.

Source: Rantala JNJ et al. Familial aggregation of early-onset cancers in early-onset breast cancer families. Int J Cancer. 2023;153(2):331-340 (Apr 19). Doi: 10.1002/ijc.34538

Key clinical point: Some relatives of women with early-onset breast cancer (BC) may have an increased risk of developing discordant early-onset cancers (other than breast cancers).

Major finding: Among relatives of women with early-onset BC, offspring had a higher risk for any discordant early-onset cancer (standardized incidence ratio [SIR] 1.27; 95% CI 1.03-1.55), siblings' children had an increased risk for early-onset testicular cancer (SIR 1.74; 95% CI 1.07-2.69) and ovarian cancer (SIR 2.69; 95% CI 1.08-5.53), and siblings had an increased risk for early-onset pancreatic cancer (SIR 7.61; 95% CI 1.57-22.23).

Study details: Findings are from an analysis of a population-based cohort including 54,753 relatives from 5562 families of females diagnosed with early-onset BC.

Disclosures: This study was funded by the Cancer Foundation Finland and Academy of Finland. The authors declared no conflicts of interest.

Source: Rantala JNJ et al. Familial aggregation of early-onset cancers in early-onset breast cancer families. Int J Cancer. 2023;153(2):331-340 (Apr 19). Doi: 10.1002/ijc.34538

Key clinical point: Some relatives of women with early-onset breast cancer (BC) may have an increased risk of developing discordant early-onset cancers (other than breast cancers).

Major finding: Among relatives of women with early-onset BC, offspring had a higher risk for any discordant early-onset cancer (standardized incidence ratio [SIR] 1.27; 95% CI 1.03-1.55), siblings' children had an increased risk for early-onset testicular cancer (SIR 1.74; 95% CI 1.07-2.69) and ovarian cancer (SIR 2.69; 95% CI 1.08-5.53), and siblings had an increased risk for early-onset pancreatic cancer (SIR 7.61; 95% CI 1.57-22.23).

Study details: Findings are from an analysis of a population-based cohort including 54,753 relatives from 5562 families of females diagnosed with early-onset BC.

Disclosures: This study was funded by the Cancer Foundation Finland and Academy of Finland. The authors declared no conflicts of interest.

Source: Rantala JNJ et al. Familial aggregation of early-onset cancers in early-onset breast cancer families. Int J Cancer. 2023;153(2):331-340 (Apr 19). Doi: 10.1002/ijc.34538

Key clinical point: Anlotinib combined with chemotherapy demonstrated good activity in the treatment of metastatic triple-negative breast cancer (TNBC) along with an acceptable safety profile in a single-arm phase 2 study.

Major finding: The median progression-free survival was 8.8 months (95% CI 6.5-11.1 months), and the median overall survival was 19.0 months (95% CI 12.1-25.9 months). Grade 3-4 treatment-related adverse events (TRAE) included neutropenia (22.5%), leukopenia (20.0%), secondary hypertension (10.0%), hand-foot syndrome (5.0%), vomiting (5.0%), proteinuria (5.0%), and thrombocytopenia (2.5%), and no deaths due to TRAE were reported.

Study details: Findings are from a prospective phase 2 trial including 40 patients with metastatic TNBC who were previously treated with anthracycline or taxane and received anlotinib combined with chemotherapy.

Disclosures: This study received funding support from the Shenzhen Basic Research Program, China, and the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Huang JY et al. A single-arm phase II clinical trial of anlotinib combined with chemotherapy for the treatment of metastatic triple-negative breast cancer. Front Oncol. 2023;13:1122294 (Apr 12). Doi: 10.3389/fonc.2023.1122294

Key clinical point: Anlotinib combined with chemotherapy demonstrated good activity in the treatment of metastatic triple-negative breast cancer (TNBC) along with an acceptable safety profile in a single-arm phase 2 study.

Major finding: The median progression-free survival was 8.8 months (95% CI 6.5-11.1 months), and the median overall survival was 19.0 months (95% CI 12.1-25.9 months). Grade 3-4 treatment-related adverse events (TRAE) included neutropenia (22.5%), leukopenia (20.0%), secondary hypertension (10.0%), hand-foot syndrome (5.0%), vomiting (5.0%), proteinuria (5.0%), and thrombocytopenia (2.5%), and no deaths due to TRAE were reported.

Study details: Findings are from a prospective phase 2 trial including 40 patients with metastatic TNBC who were previously treated with anthracycline or taxane and received anlotinib combined with chemotherapy.

Disclosures: This study received funding support from the Shenzhen Basic Research Program, China, and the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Huang JY et al. A single-arm phase II clinical trial of anlotinib combined with chemotherapy for the treatment of metastatic triple-negative breast cancer. Front Oncol. 2023;13:1122294 (Apr 12). Doi: 10.3389/fonc.2023.1122294

Key clinical point: Anlotinib combined with chemotherapy demonstrated good activity in the treatment of metastatic triple-negative breast cancer (TNBC) along with an acceptable safety profile in a single-arm phase 2 study.

Major finding: The median progression-free survival was 8.8 months (95% CI 6.5-11.1 months), and the median overall survival was 19.0 months (95% CI 12.1-25.9 months). Grade 3-4 treatment-related adverse events (TRAE) included neutropenia (22.5%), leukopenia (20.0%), secondary hypertension (10.0%), hand-foot syndrome (5.0%), vomiting (5.0%), proteinuria (5.0%), and thrombocytopenia (2.5%), and no deaths due to TRAE were reported.

Study details: Findings are from a prospective phase 2 trial including 40 patients with metastatic TNBC who were previously treated with anthracycline or taxane and received anlotinib combined with chemotherapy.

Disclosures: This study received funding support from the Shenzhen Basic Research Program, China, and the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Huang JY et al. A single-arm phase II clinical trial of anlotinib combined with chemotherapy for the treatment of metastatic triple-negative breast cancer. Front Oncol. 2023;13:1122294 (Apr 12). Doi: 10.3389/fonc.2023.1122294

Key clinical point: Targeted axillary dissection (TAD) by marking the metastatic lymph node with ¹²⁵I seeds before neoadjuvant chemotherapy (NACT) showed excellent identification rates and ruled out the need for remarking before surgery.

Major finding: The identification rates of the marked lymph node (MLN) and sentinel node (SN) were 99.3% and 91.5%, respectively, with the TAD procedure being successful in 91.5% of patients based on the identification of both MLN and SN. Overall, 40.8% of patients achieved axillary pathologic complete response and could be spared from surgery.

Study details: Findings are from a cohort study including 142 patients with BC who underwent TAD after ¹²⁵I seeds were placed before NACT.

Disclosures: This study was funded by Helsefonden. The authors did not report conflicts of interest.

Source: Munck F et al. Targeted axillary dissection with ¹²⁵I seed placement before neoadjuvant chemotherapy in a Danish multicenter cohort. Ann Surg Oncol. 2023 (Apr 16). Doi: 10.1245/s10434-023-13432-4

Key clinical point: Targeted axillary dissection (TAD) by marking the metastatic lymph node with ¹²⁵I seeds before neoadjuvant chemotherapy (NACT) showed excellent identification rates and ruled out the need for remarking before surgery.

Major finding: The identification rates of the marked lymph node (MLN) and sentinel node (SN) were 99.3% and 91.5%, respectively, with the TAD procedure being successful in 91.5% of patients based on the identification of both MLN and SN. Overall, 40.8% of patients achieved axillary pathologic complete response and could be spared from surgery.

Study details: Findings are from a cohort study including 142 patients with BC who underwent TAD after ¹²⁵I seeds were placed before NACT.

Disclosures: This study was funded by Helsefonden. The authors did not report conflicts of interest.

Source: Munck F et al. Targeted axillary dissection with ¹²⁵I seed placement before neoadjuvant chemotherapy in a Danish multicenter cohort. Ann Surg Oncol. 2023 (Apr 16). Doi: 10.1245/s10434-023-13432-4

Key clinical point: Targeted axillary dissection (TAD) by marking the metastatic lymph node with ¹²⁵I seeds before neoadjuvant chemotherapy (NACT) showed excellent identification rates and ruled out the need for remarking before surgery.

Major finding: The identification rates of the marked lymph node (MLN) and sentinel node (SN) were 99.3% and 91.5%, respectively, with the TAD procedure being successful in 91.5% of patients based on the identification of both MLN and SN. Overall, 40.8% of patients achieved axillary pathologic complete response and could be spared from surgery.

Study details: Findings are from a cohort study including 142 patients with BC who underwent TAD after ¹²⁵I seeds were placed before NACT.

Disclosures: This study was funded by Helsefonden. The authors did not report conflicts of interest.

Source: Munck F et al. Targeted axillary dissection with ¹²⁵I seed placement before neoadjuvant chemotherapy in a Danish multicenter cohort. Ann Surg Oncol. 2023 (Apr 16). Doi: 10.1245/s10434-023-13432-4

Key clinical point: Pretreatment tumor stage and nodal involvement could predict the risk for disease relapse in patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) who had achieved pathologic complete response (pCR) with neoadjuvant chemotherapy plus anti-HER2 therapy.

Major finding: Patients who did vs did not achieve pCR had prolonged event-free survival (EFS; hazard ratio [HR] 0.39) and overall survival (HR 0.32; both P < .001). However, in patients with pCR, higher pretreatment tumor stage (cT3-4 vs cT1-2; P = .007) and presence of nodal involvement (cN+ vs cN−; P = .039) could worsen EFS.

Study details: This study analyzed the data of 3710 patients with HER2+ early BC from 11 trials who had received neoadjuvant chemotherapy+anti-HER2 therapy, of which 40.4% of patients had achieved pCR.

Disclosures: This study was supported by author Sibylle Loibl. Several authors declared serving as consultants or advisors, receiving honoraria or research funding, or having other ties with various sources.

Source: van Mackelenbergh MT et al on behalf of the CTNeoBC project. Pathologic complete response and individual patient prognosis after neoadjuvant chemotherapy plus anti-human epidermal growth factor receptor 2 therapy of human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. 2023 (Apr 19). Doi: 10.1200/JCO.22.02241

Key clinical point: Pretreatment tumor stage and nodal involvement could predict the risk for disease relapse in patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) who had achieved pathologic complete response (pCR) with neoadjuvant chemotherapy plus anti-HER2 therapy.

Major finding: Patients who did vs did not achieve pCR had prolonged event-free survival (EFS; hazard ratio [HR] 0.39) and overall survival (HR 0.32; both P < .001). However, in patients with pCR, higher pretreatment tumor stage (cT3-4 vs cT1-2; P = .007) and presence of nodal involvement (cN+ vs cN−; P = .039) could worsen EFS.

Study details: This study analyzed the data of 3710 patients with HER2+ early BC from 11 trials who had received neoadjuvant chemotherapy+anti-HER2 therapy, of which 40.4% of patients had achieved pCR.

Disclosures: This study was supported by author Sibylle Loibl. Several authors declared serving as consultants or advisors, receiving honoraria or research funding, or having other ties with various sources.

Source: van Mackelenbergh MT et al on behalf of the CTNeoBC project. Pathologic complete response and individual patient prognosis after neoadjuvant chemotherapy plus anti-human epidermal growth factor receptor 2 therapy of human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. 2023 (Apr 19). Doi: 10.1200/JCO.22.02241

Key clinical point: Pretreatment tumor stage and nodal involvement could predict the risk for disease relapse in patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC) who had achieved pathologic complete response (pCR) with neoadjuvant chemotherapy plus anti-HER2 therapy.

Major finding: Patients who did vs did not achieve pCR had prolonged event-free survival (EFS; hazard ratio [HR] 0.39) and overall survival (HR 0.32; both P < .001). However, in patients with pCR, higher pretreatment tumor stage (cT3-4 vs cT1-2; P = .007) and presence of nodal involvement (cN+ vs cN−; P = .039) could worsen EFS.

Study details: This study analyzed the data of 3710 patients with HER2+ early BC from 11 trials who had received neoadjuvant chemotherapy+anti-HER2 therapy, of which 40.4% of patients had achieved pCR.

Disclosures: This study was supported by author Sibylle Loibl. Several authors declared serving as consultants or advisors, receiving honoraria or research funding, or having other ties with various sources.

Source: van Mackelenbergh MT et al on behalf of the CTNeoBC project. Pathologic complete response and individual patient prognosis after neoadjuvant chemotherapy plus anti-human epidermal growth factor receptor 2 therapy of human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. 2023 (Apr 19). Doi: 10.1200/JCO.22.02241

Key clinical point: The incidence rate of squamous cell carcinoma (SCC) was extremely low and, hence, of minimal public health concern in patients with non-SCC breast cancer (BC) or carcinoma in situ who underwent implant-based reconstruction.

Major finding: Only 1 woman was diagnosed with SCC after 52 months of BC diagnosis. The incidence rate of SCC after implant-based reconstruction was extremely low (2.37 per million person-years) and was not significantly higher in women with BC than in the general population (standardized incidence ratio 2.33; 95% CI 0.06-13.0).

Study details: Findings are from a cohort study including 56,785 women with BC or carcinoma in situ who underwent cancer-directed mastectomy with implant reconstruction.

Disclosures: This study was supported by the US National Cancer Institute. Some authors declared receiving personal fees or grants or having other ties with several sources.

Source: Kinslow CJ et al. Risk of squamous cell carcinoma of the breast following postmastectomy implant reconstruction in women with breast cancer and carcinoma in situ. JAMA Surg. 2023 (Apr 19). Doi: 10.1001/jamasurg.2023.0262 

Key clinical point: The incidence rate of squamous cell carcinoma (SCC) was extremely low and, hence, of minimal public health concern in patients with non-SCC breast cancer (BC) or carcinoma in situ who underwent implant-based reconstruction.

Major finding: Only 1 woman was diagnosed with SCC after 52 months of BC diagnosis. The incidence rate of SCC after implant-based reconstruction was extremely low (2.37 per million person-years) and was not significantly higher in women with BC than in the general population (standardized incidence ratio 2.33; 95% CI 0.06-13.0).

Study details: Findings are from a cohort study including 56,785 women with BC or carcinoma in situ who underwent cancer-directed mastectomy with implant reconstruction.

Disclosures: This study was supported by the US National Cancer Institute. Some authors declared receiving personal fees or grants or having other ties with several sources.

Source: Kinslow CJ et al. Risk of squamous cell carcinoma of the breast following postmastectomy implant reconstruction in women with breast cancer and carcinoma in situ. JAMA Surg. 2023 (Apr 19). Doi: 10.1001/jamasurg.2023.0262 

Key clinical point: The incidence rate of squamous cell carcinoma (SCC) was extremely low and, hence, of minimal public health concern in patients with non-SCC breast cancer (BC) or carcinoma in situ who underwent implant-based reconstruction.

Major finding: Only 1 woman was diagnosed with SCC after 52 months of BC diagnosis. The incidence rate of SCC after implant-based reconstruction was extremely low (2.37 per million person-years) and was not significantly higher in women with BC than in the general population (standardized incidence ratio 2.33; 95% CI 0.06-13.0).

Study details: Findings are from a cohort study including 56,785 women with BC or carcinoma in situ who underwent cancer-directed mastectomy with implant reconstruction.

Disclosures: This study was supported by the US National Cancer Institute. Some authors declared receiving personal fees or grants or having other ties with several sources.

Source: Kinslow CJ et al. Risk of squamous cell carcinoma of the breast following postmastectomy implant reconstruction in women with breast cancer and carcinoma in situ. JAMA Surg. 2023 (Apr 19). Doi: 10.1001/jamasurg.2023.0262 

Key clinical point: Adherence to the American Institute for Cancer Research and American Cancer Society’s lifestyle recommendations reduced the risk for disease recurrence and improved mortality in patients with high-risk breast cancer (BC).

Major finding: Patients in the highest vs lowest tertile of lifestyle index scores (LIS) experienced a 37% reduction in recurrence (hazard ratio [HR] 0.63; 95% CI 0.48-0.82) and those in the middle (HR 0.70; P = .03) and highest (HR 0.42; P < .001) vs lowest tertile of LIS had significant reductions in mortality.

Study details: Findings are from the prospective, observational, DELCaP (The Diet, Exercise, Lifestyles, and Cancer Prognosis) study including 1340 chemotherapy-naive women with high-risk stage I to III BC, of which the majority (65.3%) of women had hormone receptor-positive BC.

Disclosures: This study was supported by the US National Cancer Institute and The Breast Cancer Research Foundation, New York Some authors declared serving as members of independent data monitoring committees or receiving grants or personal fees from several sources.

Source: Cannioto RA et al. Adherence to cancer prevention lifestyle recommendations before, during, and 2 years after treatment for high-risk breast cancer. JAMA Netw Open. 2023;6(5):e2311673 (May 4). Doi: 10.1001/jamanetworkopen.2023.11673

Key clinical point: Adherence to the American Institute for Cancer Research and American Cancer Society’s lifestyle recommendations reduced the risk for disease recurrence and improved mortality in patients with high-risk breast cancer (BC).

Major finding: Patients in the highest vs lowest tertile of lifestyle index scores (LIS) experienced a 37% reduction in recurrence (hazard ratio [HR] 0.63; 95% CI 0.48-0.82) and those in the middle (HR 0.70; P = .03) and highest (HR 0.42; P < .001) vs lowest tertile of LIS had significant reductions in mortality.

Study details: Findings are from the prospective, observational, DELCaP (The Diet, Exercise, Lifestyles, and Cancer Prognosis) study including 1340 chemotherapy-naive women with high-risk stage I to III BC, of which the majority (65.3%) of women had hormone receptor-positive BC.

Disclosures: This study was supported by the US National Cancer Institute and The Breast Cancer Research Foundation, New York Some authors declared serving as members of independent data monitoring committees or receiving grants or personal fees from several sources.

Source: Cannioto RA et al. Adherence to cancer prevention lifestyle recommendations before, during, and 2 years after treatment for high-risk breast cancer. JAMA Netw Open. 2023;6(5):e2311673 (May 4). Doi: 10.1001/jamanetworkopen.2023.11673

Key clinical point: Adherence to the American Institute for Cancer Research and American Cancer Society’s lifestyle recommendations reduced the risk for disease recurrence and improved mortality in patients with high-risk breast cancer (BC).

Major finding: Patients in the highest vs lowest tertile of lifestyle index scores (LIS) experienced a 37% reduction in recurrence (hazard ratio [HR] 0.63; 95% CI 0.48-0.82) and those in the middle (HR 0.70; P = .03) and highest (HR 0.42; P < .001) vs lowest tertile of LIS had significant reductions in mortality.

Study details: Findings are from the prospective, observational, DELCaP (The Diet, Exercise, Lifestyles, and Cancer Prognosis) study including 1340 chemotherapy-naive women with high-risk stage I to III BC, of which the majority (65.3%) of women had hormone receptor-positive BC.

Disclosures: This study was supported by the US National Cancer Institute and The Breast Cancer Research Foundation, New York Some authors declared serving as members of independent data monitoring committees or receiving grants or personal fees from several sources.

Source: Cannioto RA et al. Adherence to cancer prevention lifestyle recommendations before, during, and 2 years after treatment for high-risk breast cancer. JAMA Netw Open. 2023;6(5):e2311673 (May 4). Doi: 10.1001/jamanetworkopen.2023.11673

Key clinical point: Breast cancer (BC) recurrence rates are lower among patients treated with the combination of anthracycline and taxane compared with a taxane regimen without anthracycline or an anthracycline-based regimen without taxane.

Major finding: Anthracycline plus taxane reduced the rate of BC recurrence by 14% (rate ratio [RR] 0.86; P = .0004) compared with taxane only and by 13% (RR 0.87; P < .0001) compared with anthracycline only. The highest benefit was observed among patients receiving anthracycline concurrently with docetaxel+cyclophosphamide vs docetaxel+cyclophosphamide only (RR 0.58; P < .0001).

Study details: Findings are from a meta-analysis including more than 100,000 women with early-stage BC from 86 trials on anthracycline- and taxane-based chemotherapies.

Disclosures: This study is funded by Cancer Research UK. The authors declared receiving grants, payments, honoraria, consulting fees, or travel support from or having other ties with various sources.

Source: Early Breast Cancer Trialists' Collaborative Group. Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: A patient-level meta-analysis of 100 000 women from 86 randomised trials. Lancet. 2023;401(10384):1277-1292 (Apr 15). Doi: 10.1016/S0140-6736(23)00285-4

Key clinical point: Breast cancer (BC) recurrence rates are lower among patients treated with the combination of anthracycline and taxane compared with a taxane regimen without anthracycline or an anthracycline-based regimen without taxane.

Major finding: Anthracycline plus taxane reduced the rate of BC recurrence by 14% (rate ratio [RR] 0.86; P = .0004) compared with taxane only and by 13% (RR 0.87; P < .0001) compared with anthracycline only. The highest benefit was observed among patients receiving anthracycline concurrently with docetaxel+cyclophosphamide vs docetaxel+cyclophosphamide only (RR 0.58; P < .0001).

Study details: Findings are from a meta-analysis including more than 100,000 women with early-stage BC from 86 trials on anthracycline- and taxane-based chemotherapies.

Disclosures: This study is funded by Cancer Research UK. The authors declared receiving grants, payments, honoraria, consulting fees, or travel support from or having other ties with various sources.

Source: Early Breast Cancer Trialists' Collaborative Group. Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: A patient-level meta-analysis of 100 000 women from 86 randomised trials. Lancet. 2023;401(10384):1277-1292 (Apr 15). Doi: 10.1016/S0140-6736(23)00285-4

Key clinical point: Breast cancer (BC) recurrence rates are lower among patients treated with the combination of anthracycline and taxane compared with a taxane regimen without anthracycline or an anthracycline-based regimen without taxane.

Major finding: Anthracycline plus taxane reduced the rate of BC recurrence by 14% (rate ratio [RR] 0.86; P = .0004) compared with taxane only and by 13% (RR 0.87; P < .0001) compared with anthracycline only. The highest benefit was observed among patients receiving anthracycline concurrently with docetaxel+cyclophosphamide vs docetaxel+cyclophosphamide only (RR 0.58; P < .0001).

Study details: Findings are from a meta-analysis including more than 100,000 women with early-stage BC from 86 trials on anthracycline- and taxane-based chemotherapies.

Disclosures: This study is funded by Cancer Research UK. The authors declared receiving grants, payments, honoraria, consulting fees, or travel support from or having other ties with various sources.

Source: Early Breast Cancer Trialists' Collaborative Group. Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: A patient-level meta-analysis of 100 000 women from 86 randomised trials. Lancet. 2023;401(10384):1277-1292 (Apr 15). Doi: 10.1016/S0140-6736(23)00285-4

Having a fatty liver raises a patient’s risk of colorectal cancer liver metastasis via an immunosuppressive tumor microenvironment, yes-associated protein (YAP) signaling, and extracellular vesicle-microRNAs, according to the authors of new research.

These findings support the previously reported link between fatty liver and colorectal cancer (CRC) liver metastasis, and suggest that CRC patients with nonalcoholic fatty liver disease (NAFLD) may respond differently to treatment than CRC patients without NAFLD, wrote lead author Zhijun Wang, MD, PhD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues, in their paper.

“Obesity and NAFLD are the significant risk factors for CRC,” the investigators explained, in Cell Metabolism. “A growing body of epidemiological evidence indicates that fatty liver increases the occurrence of CRC liver metastasis and the local recurrence after resection of CRC liver metastases, thereby worsening prognosis ... There is an urgent need to understand the molecular mechanisms of metastasis in patients with fatty liver to manage those patients effectively.”

To this end, Dr. Wang and colleagues conducted a series of experiments involving mice, cell cultures, and human sera. They found that fatty liver increases risk of CRC liver metastasis via extracellular vesicles (EVs) that contain procarcinogenic miRNAs. As these EVs transfer microRNAs from fatty liver hepatocytes to metastatic cancer cells, YAP activity increases, which, in turn, suppresses immune activity within the tumor microenvironment, promoting growth of CRC metastasis.

Beyond the increased risk of liver metastasis presented by fatty liver, the investigators suggested that NAFLD may cause “more complex” metastatic tumor microenvironments, potentially explaining “diverse responses” to cancer therapies among patients with CRC and liver metastases.

“In summary, our study demonstrates that the pre- and prometastatic liver environment of fatty liver is induced by procarcinogenic EVs and results in an immunosuppressive tumor microenvironemnt, in which YAP plays an important role,” the investigators concluded. “Our study provides new insight into [the] distinct liver tumor microenvironment in patients with fatty liver and without fatty liver, which may contribute to the aggressiveness of metastatic tumors and weak responses to anticancer therapy in patients with fatty liver. Additional studies are warranted to develop precision medicine for treating patients with CRC and liver metastasis.”

One of the study authors disclosed relationships with Altimmune, Cytodyn, Novo Nordisk, and others. The other investigators had no relevant financial disclosures.

Having a fatty liver raises a patient’s risk of colorectal cancer liver metastasis via an immunosuppressive tumor microenvironment, yes-associated protein (YAP) signaling, and extracellular vesicle-microRNAs, according to the authors of new research.

These findings support the previously reported link between fatty liver and colorectal cancer (CRC) liver metastasis, and suggest that CRC patients with nonalcoholic fatty liver disease (NAFLD) may respond differently to treatment than CRC patients without NAFLD, wrote lead author Zhijun Wang, MD, PhD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues, in their paper.

“Obesity and NAFLD are the significant risk factors for CRC,” the investigators explained, in Cell Metabolism. “A growing body of epidemiological evidence indicates that fatty liver increases the occurrence of CRC liver metastasis and the local recurrence after resection of CRC liver metastases, thereby worsening prognosis ... There is an urgent need to understand the molecular mechanisms of metastasis in patients with fatty liver to manage those patients effectively.”

To this end, Dr. Wang and colleagues conducted a series of experiments involving mice, cell cultures, and human sera. They found that fatty liver increases risk of CRC liver metastasis via extracellular vesicles (EVs) that contain procarcinogenic miRNAs. As these EVs transfer microRNAs from fatty liver hepatocytes to metastatic cancer cells, YAP activity increases, which, in turn, suppresses immune activity within the tumor microenvironment, promoting growth of CRC metastasis.

Beyond the increased risk of liver metastasis presented by fatty liver, the investigators suggested that NAFLD may cause “more complex” metastatic tumor microenvironments, potentially explaining “diverse responses” to cancer therapies among patients with CRC and liver metastases.

“In summary, our study demonstrates that the pre- and prometastatic liver environment of fatty liver is induced by procarcinogenic EVs and results in an immunosuppressive tumor microenvironemnt, in which YAP plays an important role,” the investigators concluded. “Our study provides new insight into [the] distinct liver tumor microenvironment in patients with fatty liver and without fatty liver, which may contribute to the aggressiveness of metastatic tumors and weak responses to anticancer therapy in patients with fatty liver. Additional studies are warranted to develop precision medicine for treating patients with CRC and liver metastasis.”

One of the study authors disclosed relationships with Altimmune, Cytodyn, Novo Nordisk, and others. The other investigators had no relevant financial disclosures.

Having a fatty liver raises a patient’s risk of colorectal cancer liver metastasis via an immunosuppressive tumor microenvironment, yes-associated protein (YAP) signaling, and extracellular vesicle-microRNAs, according to the authors of new research.

These findings support the previously reported link between fatty liver and colorectal cancer (CRC) liver metastasis, and suggest that CRC patients with nonalcoholic fatty liver disease (NAFLD) may respond differently to treatment than CRC patients without NAFLD, wrote lead author Zhijun Wang, MD, PhD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues, in their paper.

“Obesity and NAFLD are the significant risk factors for CRC,” the investigators explained, in Cell Metabolism. “A growing body of epidemiological evidence indicates that fatty liver increases the occurrence of CRC liver metastasis and the local recurrence after resection of CRC liver metastases, thereby worsening prognosis ... There is an urgent need to understand the molecular mechanisms of metastasis in patients with fatty liver to manage those patients effectively.”

To this end, Dr. Wang and colleagues conducted a series of experiments involving mice, cell cultures, and human sera. They found that fatty liver increases risk of CRC liver metastasis via extracellular vesicles (EVs) that contain procarcinogenic miRNAs. As these EVs transfer microRNAs from fatty liver hepatocytes to metastatic cancer cells, YAP activity increases, which, in turn, suppresses immune activity within the tumor microenvironment, promoting growth of CRC metastasis.

Beyond the increased risk of liver metastasis presented by fatty liver, the investigators suggested that NAFLD may cause “more complex” metastatic tumor microenvironments, potentially explaining “diverse responses” to cancer therapies among patients with CRC and liver metastases.

“In summary, our study demonstrates that the pre- and prometastatic liver environment of fatty liver is induced by procarcinogenic EVs and results in an immunosuppressive tumor microenvironemnt, in which YAP plays an important role,” the investigators concluded. “Our study provides new insight into [the] distinct liver tumor microenvironment in patients with fatty liver and without fatty liver, which may contribute to the aggressiveness of metastatic tumors and weak responses to anticancer therapy in patients with fatty liver. Additional studies are warranted to develop precision medicine for treating patients with CRC and liver metastasis.”

One of the study authors disclosed relationships with Altimmune, Cytodyn, Novo Nordisk, and others. The other investigators had no relevant financial disclosures.

Key clinical point: Temporarily discontinuing endocrine therapy (ET) to attempt pregnancy did not increase the recurrence risk for breast cancer (BC) in young women with early hormone receptor-positive (HR+) BC.

Major finding: After a median follow-up of 41 months, 44 patients had BC and the incidence of BC events was not higher among patients who interrupted ET vs control individuals with BC from an external cohort who received treatment with different adjuvant endocrine strategies (hazard ratio 0.81; 95% CI 0.57-1.15). Pregnancy was reported by 368 patients and 317 patients had ≥1 live birth.

Study details: Findings are from a single-group trial including 516 premenopausal women aged ≤42 years with stage I, II, or III HR+ BC treated with ET for 18-30 months who discontinued ET to attempt pregnancy.

Disclosures: This study was supported by the ETOP IBCSG Partners Foundation and other sources. Some authors declared serving as consultants; receiving grants, contracts, or travel support; or having other ties with several sources.

Source: Partridge AH et al for the International Breast Cancer Study Group, and the POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388(18):1645-1656 (May 4). Doi: 10.1056/NEJMoa2212856

Key clinical point: Temporarily discontinuing endocrine therapy (ET) to attempt pregnancy did not increase the recurrence risk for breast cancer (BC) in young women with early hormone receptor-positive (HR+) BC.

Major finding: After a median follow-up of 41 months, 44 patients had BC and the incidence of BC events was not higher among patients who interrupted ET vs control individuals with BC from an external cohort who received treatment with different adjuvant endocrine strategies (hazard ratio 0.81; 95% CI 0.57-1.15). Pregnancy was reported by 368 patients and 317 patients had ≥1 live birth.

Study details: Findings are from a single-group trial including 516 premenopausal women aged ≤42 years with stage I, II, or III HR+ BC treated with ET for 18-30 months who discontinued ET to attempt pregnancy.

Disclosures: This study was supported by the ETOP IBCSG Partners Foundation and other sources. Some authors declared serving as consultants; receiving grants, contracts, or travel support; or having other ties with several sources.

Source: Partridge AH et al for the International Breast Cancer Study Group, and the POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388(18):1645-1656 (May 4). Doi: 10.1056/NEJMoa2212856

Key clinical point: Temporarily discontinuing endocrine therapy (ET) to attempt pregnancy did not increase the recurrence risk for breast cancer (BC) in young women with early hormone receptor-positive (HR+) BC.

Major finding: After a median follow-up of 41 months, 44 patients had BC and the incidence of BC events was not higher among patients who interrupted ET vs control individuals with BC from an external cohort who received treatment with different adjuvant endocrine strategies (hazard ratio 0.81; 95% CI 0.57-1.15). Pregnancy was reported by 368 patients and 317 patients had ≥1 live birth.

Study details: Findings are from a single-group trial including 516 premenopausal women aged ≤42 years with stage I, II, or III HR+ BC treated with ET for 18-30 months who discontinued ET to attempt pregnancy.

Disclosures: This study was supported by the ETOP IBCSG Partners Foundation and other sources. Some authors declared serving as consultants; receiving grants, contracts, or travel support; or having other ties with several sources.

Source: Partridge AH et al for the International Breast Cancer Study Group, and the POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388(18):1645-1656 (May 4). Doi: 10.1056/NEJMoa2212856

To the Editor:

A 67-year-old woman presented to the hospital with painful hands and feet. Two weeks prior, the patient experienced a few days of intermittent purple discoloration of the fingers, followed by black discoloration of the fingers, toes, and nose with notable pain. She reported no illness preceding the presenting symptoms, and there was no progression of symptoms in the days preceding presentation.

The patient had a history of smoking. She had a medical history of chronic obstructive pulmonary disease as well as recurrent non–small cell lung cancer that was treated most recently with a 1-year course of the programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor durvalumab (last treatment was 4 months prior to the current presentation).

Physical examination revealed necrosis of the tips of the second, third, and fourth fingers of the left hand, as well as the tips of the third and fourth fingers of the right hand, progressing to purpura proximally on all involved fingers (Figure, A); scattered purpura and necrotic papules on the toe pads (Figure, B); and a 2- to 3-cm black plaque on the nasal tip. The patient was afebrile.

An embolic and vascular workup was performed. Transthoracic echocardiography was negative for thrombi, ankle brachial indices were within reference range, and computed tomography angiography revealed a few nonocclusive coronary plaques. Conventional angiography was not performed.

Laboratory testing revealed a mildly elevated level of cryofibrinogens (cryocrit, 2.5%); cold agglutinins (1:32); mild monoclonal κ IgG gammopathy (0.1 g/dL); and elevated inflammatory markers (C-reactive protein, 76 mg/L [reference range, 0–10 mg/L]; erythrocyte sedimentation rate, 38 mm/h [reference range, 0–20 mm/h]; fibrinogen, 571 mg/dL [reference range, 150–450 mg/dL]; and ferritin, 394 ng/mL [reference range, 10–180 ng/mL]). Additional laboratory studies were negative or within reference range, including tests of anti-RNA polymerase antibody, rheumatoid factor, antinuclear antibody, anticardiolipin antibody, anti-β₂ glycoprotein antibody, antineutrophil cytoplasmic antibodies (myeloperoxidase and proteinase-3), cryoglobulins, and complement; human immunodeficiency virus and hepatitis B and C virus serologic studies; prothrombin time, partial thromboplastin time, and lupus anticoagulant; and a heparin-induced thrombocytopenia panel.

A skin biopsy adjacent to an area of necrosis on the finger showed thickened walls of dermal vessels, sparse leukocytoclastic debris, and evidence of recanalizing medium-sized vessels. Direct immunofluorescence studies were negative.

Based on the clinical history and histologic findings showing an absence of vasculitis, a diagnosis of acral necrosis associated with the PD-L1 immune checkpoint inhibitor durvalumab—a delayed immune-related event (DIRE)—was favored. The calcium channel blocker amlodipine was started at a dosage of 2.5 mg/d orally. Necrosis of the toes resolved over the course of 1 week; however, necrosis of the fingers remained unchanged. After 1 week of hospitalization, the patient was discharged at her request.

Acral necrosis following immune checkpoint inhibitor therapy has been reported as a rare and recalcitrant immune-related adverse event (AE).^1-4 However, our patient’s symptoms occurred months after treatment was discontinued, which is consistent with a DIRE.⁵ The course of acral necrosis begins with acrocyanosis (a Raynaud disease–like phenomenon) of the fingers that progresses to necrosis. A history of Raynaud disease or other autoimmune disorder generally is absent.¹ Our patient’s history indicated actively smoking at the time of presentation, similar to a case described by Khaddour et al.¹ Similarly, in a case presented by Comont et al,³ the patient also had a history of smoking. In a recent study of acute vascular events associated with immune checkpoint inhibitors, 16 of 31 patients had a history of smoking.⁶

No definitive diagnostic laboratory or pathologic findings are associated with acral necrosis following immune checkpoint inhibitor therapy. Histopathologic analysis does not demonstrate vasculitis or other overt vascular pathology.^2,3

The optimal treatment of immune checkpoint inhibitor–associated digital necrosis is unclear. Corticosteroids and discontinuation of the immune checkpoint inhibitor generally are employed,^1-4 though treatment response has been variable. Other therapies such as calcium channel blockers (as in our case), sympathectomy,¹ epoprostenol, botulinum injection, rituximab,² and alprostadil⁴ have been attempted without clear effect.

We considered a diagnosis of paraneoplastic acral vascular syndrome in our patient, which was ruled out because the syndrome typically occurs in the setting of a worsening underlying malignancy⁷; our patient’s cancer was stable to improved. Thromboangiitis obliterans was ruled out by the absence of a characteristic thrombus on biopsy, the patient’s older age, and involvement of the nose.

We report an unusual case of acral necrosis occurring as a DIRE in response to administration of an immune checkpoint inhibitor. Further description is needed to clarify the diagnostic criteria for and treatment of this rare autoimmune phenomenon.

To the Editor:

A 67-year-old woman presented to the hospital with painful hands and feet. Two weeks prior, the patient experienced a few days of intermittent purple discoloration of the fingers, followed by black discoloration of the fingers, toes, and nose with notable pain. She reported no illness preceding the presenting symptoms, and there was no progression of symptoms in the days preceding presentation.

The patient had a history of smoking. She had a medical history of chronic obstructive pulmonary disease as well as recurrent non–small cell lung cancer that was treated most recently with a 1-year course of the programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor durvalumab (last treatment was 4 months prior to the current presentation).

Physical examination revealed necrosis of the tips of the second, third, and fourth fingers of the left hand, as well as the tips of the third and fourth fingers of the right hand, progressing to purpura proximally on all involved fingers (Figure, A); scattered purpura and necrotic papules on the toe pads (Figure, B); and a 2- to 3-cm black plaque on the nasal tip. The patient was afebrile.

An embolic and vascular workup was performed. Transthoracic echocardiography was negative for thrombi, ankle brachial indices were within reference range, and computed tomography angiography revealed a few nonocclusive coronary plaques. Conventional angiography was not performed.

Laboratory testing revealed a mildly elevated level of cryofibrinogens (cryocrit, 2.5%); cold agglutinins (1:32); mild monoclonal κ IgG gammopathy (0.1 g/dL); and elevated inflammatory markers (C-reactive protein, 76 mg/L [reference range, 0–10 mg/L]; erythrocyte sedimentation rate, 38 mm/h [reference range, 0–20 mm/h]; fibrinogen, 571 mg/dL [reference range, 150–450 mg/dL]; and ferritin, 394 ng/mL [reference range, 10–180 ng/mL]). Additional laboratory studies were negative or within reference range, including tests of anti-RNA polymerase antibody, rheumatoid factor, antinuclear antibody, anticardiolipin antibody, anti-β₂ glycoprotein antibody, antineutrophil cytoplasmic antibodies (myeloperoxidase and proteinase-3), cryoglobulins, and complement; human immunodeficiency virus and hepatitis B and C virus serologic studies; prothrombin time, partial thromboplastin time, and lupus anticoagulant; and a heparin-induced thrombocytopenia panel.

A skin biopsy adjacent to an area of necrosis on the finger showed thickened walls of dermal vessels, sparse leukocytoclastic debris, and evidence of recanalizing medium-sized vessels. Direct immunofluorescence studies were negative.

Based on the clinical history and histologic findings showing an absence of vasculitis, a diagnosis of acral necrosis associated with the PD-L1 immune checkpoint inhibitor durvalumab—a delayed immune-related event (DIRE)—was favored. The calcium channel blocker amlodipine was started at a dosage of 2.5 mg/d orally. Necrosis of the toes resolved over the course of 1 week; however, necrosis of the fingers remained unchanged. After 1 week of hospitalization, the patient was discharged at her request.

Acral necrosis following immune checkpoint inhibitor therapy has been reported as a rare and recalcitrant immune-related adverse event (AE).^1-4 However, our patient’s symptoms occurred months after treatment was discontinued, which is consistent with a DIRE.⁵ The course of acral necrosis begins with acrocyanosis (a Raynaud disease–like phenomenon) of the fingers that progresses to necrosis. A history of Raynaud disease or other autoimmune disorder generally is absent.¹ Our patient’s history indicated actively smoking at the time of presentation, similar to a case described by Khaddour et al.¹ Similarly, in a case presented by Comont et al,³ the patient also had a history of smoking. In a recent study of acute vascular events associated with immune checkpoint inhibitors, 16 of 31 patients had a history of smoking.⁶

No definitive diagnostic laboratory or pathologic findings are associated with acral necrosis following immune checkpoint inhibitor therapy. Histopathologic analysis does not demonstrate vasculitis or other overt vascular pathology.^2,3

The optimal treatment of immune checkpoint inhibitor–associated digital necrosis is unclear. Corticosteroids and discontinuation of the immune checkpoint inhibitor generally are employed,^1-4 though treatment response has been variable. Other therapies such as calcium channel blockers (as in our case), sympathectomy,¹ epoprostenol, botulinum injection, rituximab,² and alprostadil⁴ have been attempted without clear effect.

We considered a diagnosis of paraneoplastic acral vascular syndrome in our patient, which was ruled out because the syndrome typically occurs in the setting of a worsening underlying malignancy⁷; our patient’s cancer was stable to improved. Thromboangiitis obliterans was ruled out by the absence of a characteristic thrombus on biopsy, the patient’s older age, and involvement of the nose.

We report an unusual case of acral necrosis occurring as a DIRE in response to administration of an immune checkpoint inhibitor. Further description is needed to clarify the diagnostic criteria for and treatment of this rare autoimmune phenomenon.

To the Editor:

A 67-year-old woman presented to the hospital with painful hands and feet. Two weeks prior, the patient experienced a few days of intermittent purple discoloration of the fingers, followed by black discoloration of the fingers, toes, and nose with notable pain. She reported no illness preceding the presenting symptoms, and there was no progression of symptoms in the days preceding presentation.

The patient had a history of smoking. She had a medical history of chronic obstructive pulmonary disease as well as recurrent non–small cell lung cancer that was treated most recently with a 1-year course of the programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor durvalumab (last treatment was 4 months prior to the current presentation).

Physical examination revealed necrosis of the tips of the second, third, and fourth fingers of the left hand, as well as the tips of the third and fourth fingers of the right hand, progressing to purpura proximally on all involved fingers (Figure, A); scattered purpura and necrotic papules on the toe pads (Figure, B); and a 2- to 3-cm black plaque on the nasal tip. The patient was afebrile.

An embolic and vascular workup was performed. Transthoracic echocardiography was negative for thrombi, ankle brachial indices were within reference range, and computed tomography angiography revealed a few nonocclusive coronary plaques. Conventional angiography was not performed.

Laboratory testing revealed a mildly elevated level of cryofibrinogens (cryocrit, 2.5%); cold agglutinins (1:32); mild monoclonal κ IgG gammopathy (0.1 g/dL); and elevated inflammatory markers (C-reactive protein, 76 mg/L [reference range, 0–10 mg/L]; erythrocyte sedimentation rate, 38 mm/h [reference range, 0–20 mm/h]; fibrinogen, 571 mg/dL [reference range, 150–450 mg/dL]; and ferritin, 394 ng/mL [reference range, 10–180 ng/mL]). Additional laboratory studies were negative or within reference range, including tests of anti-RNA polymerase antibody, rheumatoid factor, antinuclear antibody, anticardiolipin antibody, anti-β₂ glycoprotein antibody, antineutrophil cytoplasmic antibodies (myeloperoxidase and proteinase-3), cryoglobulins, and complement; human immunodeficiency virus and hepatitis B and C virus serologic studies; prothrombin time, partial thromboplastin time, and lupus anticoagulant; and a heparin-induced thrombocytopenia panel.

A skin biopsy adjacent to an area of necrosis on the finger showed thickened walls of dermal vessels, sparse leukocytoclastic debris, and evidence of recanalizing medium-sized vessels. Direct immunofluorescence studies were negative.

Based on the clinical history and histologic findings showing an absence of vasculitis, a diagnosis of acral necrosis associated with the PD-L1 immune checkpoint inhibitor durvalumab—a delayed immune-related event (DIRE)—was favored. The calcium channel blocker amlodipine was started at a dosage of 2.5 mg/d orally. Necrosis of the toes resolved over the course of 1 week; however, necrosis of the fingers remained unchanged. After 1 week of hospitalization, the patient was discharged at her request.

Acral necrosis following immune checkpoint inhibitor therapy has been reported as a rare and recalcitrant immune-related adverse event (AE).^1-4 However, our patient’s symptoms occurred months after treatment was discontinued, which is consistent with a DIRE.⁵ The course of acral necrosis begins with acrocyanosis (a Raynaud disease–like phenomenon) of the fingers that progresses to necrosis. A history of Raynaud disease or other autoimmune disorder generally is absent.¹ Our patient’s history indicated actively smoking at the time of presentation, similar to a case described by Khaddour et al.¹ Similarly, in a case presented by Comont et al,³ the patient also had a history of smoking. In a recent study of acute vascular events associated with immune checkpoint inhibitors, 16 of 31 patients had a history of smoking.⁶

No definitive diagnostic laboratory or pathologic findings are associated with acral necrosis following immune checkpoint inhibitor therapy. Histopathologic analysis does not demonstrate vasculitis or other overt vascular pathology.^2,3

The optimal treatment of immune checkpoint inhibitor–associated digital necrosis is unclear. Corticosteroids and discontinuation of the immune checkpoint inhibitor generally are employed,^1-4 though treatment response has been variable. Other therapies such as calcium channel blockers (as in our case), sympathectomy,¹ epoprostenol, botulinum injection, rituximab,² and alprostadil⁴ have been attempted without clear effect.

We considered a diagnosis of paraneoplastic acral vascular syndrome in our patient, which was ruled out because the syndrome typically occurs in the setting of a worsening underlying malignancy⁷; our patient’s cancer was stable to improved. Thromboangiitis obliterans was ruled out by the absence of a characteristic thrombus on biopsy, the patient’s older age, and involvement of the nose.

We report an unusual case of acral necrosis occurring as a DIRE in response to administration of an immune checkpoint inhibitor. Further description is needed to clarify the diagnostic criteria for and treatment of this rare autoimmune phenomenon.