Breast Cancer

Key clinical point: Oral selective estrogen receptor degraders (SERD) improved the progression-free survival (PFS) outcomes in patients with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (BC), particularly in those with ESR1 mutations.

Major finding: Compared with endocrine therapies (ET) of the physician’s choice, oral SERD led to a greater improvement in PFS outcomes in the overall population (hazard ratio [HR] 0.783; P < .001) and in the subgroup of patients with ESR1 mutations (HR 0.557; P < .001); however, no PFS benefit was observed in the ESR1 wild-type subgroup (P  =  .543).

Study details: Findings are from a meta-analysis of individual patient data from four randomized clinical trials including 1290 patients with ER+/HER2− metastatic BC who received oral SERD or ET of physician’s choice.

Disclosures: This study did not receive any specific funding. Some authors declared receiving honoraria, research funding, or travel grants from or serving in advisory or consulting roles for various sources.

Source: Wong NZH et al. Efficacy of oral SERDs in the treatment of ER+, HER2 - metastatic breast cancer, a stratified analysis of the ESR1 wild type and mutant subgroups. Ann Oncol. 2023 (Oct 21). doi: 10.1016/j.annonc.2023.10.122

Key clinical point: Oral selective estrogen receptor degraders (SERD) improved the progression-free survival (PFS) outcomes in patients with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (BC), particularly in those with ESR1 mutations.

Major finding: Compared with endocrine therapies (ET) of the physician’s choice, oral SERD led to a greater improvement in PFS outcomes in the overall population (hazard ratio [HR] 0.783; P < .001) and in the subgroup of patients with ESR1 mutations (HR 0.557; P < .001); however, no PFS benefit was observed in the ESR1 wild-type subgroup (P  =  .543).

Study details: Findings are from a meta-analysis of individual patient data from four randomized clinical trials including 1290 patients with ER+/HER2− metastatic BC who received oral SERD or ET of physician’s choice.

Disclosures: This study did not receive any specific funding. Some authors declared receiving honoraria, research funding, or travel grants from or serving in advisory or consulting roles for various sources.

Source: Wong NZH et al. Efficacy of oral SERDs in the treatment of ER+, HER2 - metastatic breast cancer, a stratified analysis of the ESR1 wild type and mutant subgroups. Ann Oncol. 2023 (Oct 21). doi: 10.1016/j.annonc.2023.10.122

Key clinical point: Oral selective estrogen receptor degraders (SERD) improved the progression-free survival (PFS) outcomes in patients with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (BC), particularly in those with ESR1 mutations.

Major finding: Compared with endocrine therapies (ET) of the physician’s choice, oral SERD led to a greater improvement in PFS outcomes in the overall population (hazard ratio [HR] 0.783; P < .001) and in the subgroup of patients with ESR1 mutations (HR 0.557; P < .001); however, no PFS benefit was observed in the ESR1 wild-type subgroup (P  =  .543).

Study details: Findings are from a meta-analysis of individual patient data from four randomized clinical trials including 1290 patients with ER+/HER2− metastatic BC who received oral SERD or ET of physician’s choice.

Disclosures: This study did not receive any specific funding. Some authors declared receiving honoraria, research funding, or travel grants from or serving in advisory or consulting roles for various sources.

Source: Wong NZH et al. Efficacy of oral SERDs in the treatment of ER+, HER2 - metastatic breast cancer, a stratified analysis of the ESR1 wild type and mutant subgroups. Ann Oncol. 2023 (Oct 21). doi: 10.1016/j.annonc.2023.10.122

Key clinical point: Neoadjuvant immunotherapy with camrelizumab plus chemotherapy with nab-paclitaxel and epirubicin showed promising anti-tumor activity and a manageable safety profile in patients with early triple-negative breast cancer (TNBC).

Major finding: The majority of patients achieved a pathological complete response rate (64.1%; 95% CI 47.2%-78.8%) and an objective response rate (89.7%; 95% CI 74.8%-96.7%). Decreased white blood cell (56.4%), neutropenia (41.0%), and anemia (20.5%) were the most common grade 3 or 4 adverse events, and no treatment-related deaths were reported.

Study details: This phase 2 trial included 39 treatment-naive patients with early TNBC who received neoadjuvant camrelizumab, nab-paclitaxel, and epirubicin every 3 weeks for 6 cycles.

Disclosures: This study was supported by Jiangsu Hengrui Pharmaceuticals Co., Ltd, China. The authors declared no conflicts of interest.

Source: Wang C et al. Neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin in early triple-negative breast cancer: A single-arm phase II trial. Nat Commun. 2023;14:6654 (Oct 20). doi: 10.1038/s41467-023-42479-w

Key clinical point: Neoadjuvant immunotherapy with camrelizumab plus chemotherapy with nab-paclitaxel and epirubicin showed promising anti-tumor activity and a manageable safety profile in patients with early triple-negative breast cancer (TNBC).

Major finding: The majority of patients achieved a pathological complete response rate (64.1%; 95% CI 47.2%-78.8%) and an objective response rate (89.7%; 95% CI 74.8%-96.7%). Decreased white blood cell (56.4%), neutropenia (41.0%), and anemia (20.5%) were the most common grade 3 or 4 adverse events, and no treatment-related deaths were reported.

Study details: This phase 2 trial included 39 treatment-naive patients with early TNBC who received neoadjuvant camrelizumab, nab-paclitaxel, and epirubicin every 3 weeks for 6 cycles.

Disclosures: This study was supported by Jiangsu Hengrui Pharmaceuticals Co., Ltd, China. The authors declared no conflicts of interest.

Source: Wang C et al. Neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin in early triple-negative breast cancer: A single-arm phase II trial. Nat Commun. 2023;14:6654 (Oct 20). doi: 10.1038/s41467-023-42479-w

Key clinical point: Neoadjuvant immunotherapy with camrelizumab plus chemotherapy with nab-paclitaxel and epirubicin showed promising anti-tumor activity and a manageable safety profile in patients with early triple-negative breast cancer (TNBC).

Major finding: The majority of patients achieved a pathological complete response rate (64.1%; 95% CI 47.2%-78.8%) and an objective response rate (89.7%; 95% CI 74.8%-96.7%). Decreased white blood cell (56.4%), neutropenia (41.0%), and anemia (20.5%) were the most common grade 3 or 4 adverse events, and no treatment-related deaths were reported.

Study details: This phase 2 trial included 39 treatment-naive patients with early TNBC who received neoadjuvant camrelizumab, nab-paclitaxel, and epirubicin every 3 weeks for 6 cycles.

Disclosures: This study was supported by Jiangsu Hengrui Pharmaceuticals Co., Ltd, China. The authors declared no conflicts of interest.

Source: Wang C et al. Neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin in early triple-negative breast cancer: A single-arm phase II trial. Nat Commun. 2023;14:6654 (Oct 20). doi: 10.1038/s41467-023-42479-w

Key clinical point: Premenopausal women with invasive lobular carcinoma (ILC) vs invasive ductal carcinoma (IDC) had better breast cancer-specific survival (BCSS) outcomes within 10 years after disease diagnosis, but the prognosis worsened in the long run.

Major finding: In the Surveillance, Epidemiology, and End Results (SEER) database, patients with ILC vs IDC showed improved BCSS outcomes during the first 10 years after diagnosis (hazard ratio [HR] 0.73; P < .001); however, after 10 years, the trend reversed and BCSS outcomes worsened by 80% in patients with ILC (HR 1.80; P < .001). ILC was also associated with worsened long-term prognosis in patients from the Korean Breast Cancer Registry and Asan Medical Center Research database.

Study details: This retrospective cohort study analyzed the data from three databases and included 225,938 premenopausal women (age < 50 years) with stages I-III ILC or IDC.

Disclosures: This study was supported by a grant from the Korea Health Technology R&D Project. O Metzger declared receiving grant funding and personal fees from various sources.

Source: Yoon TI et al. Survival outcomes in premenopausal patients with invasive lobular carcinoma. JAMA Netw Open. 2023;6(11):e2342270 (Nov 8). doi: 10.1001/jamanetworkopen.2023.42270

Key clinical point: Premenopausal women with invasive lobular carcinoma (ILC) vs invasive ductal carcinoma (IDC) had better breast cancer-specific survival (BCSS) outcomes within 10 years after disease diagnosis, but the prognosis worsened in the long run.

Major finding: In the Surveillance, Epidemiology, and End Results (SEER) database, patients with ILC vs IDC showed improved BCSS outcomes during the first 10 years after diagnosis (hazard ratio [HR] 0.73; P < .001); however, after 10 years, the trend reversed and BCSS outcomes worsened by 80% in patients with ILC (HR 1.80; P < .001). ILC was also associated with worsened long-term prognosis in patients from the Korean Breast Cancer Registry and Asan Medical Center Research database.

Study details: This retrospective cohort study analyzed the data from three databases and included 225,938 premenopausal women (age < 50 years) with stages I-III ILC or IDC.

Disclosures: This study was supported by a grant from the Korea Health Technology R&D Project. O Metzger declared receiving grant funding and personal fees from various sources.

Source: Yoon TI et al. Survival outcomes in premenopausal patients with invasive lobular carcinoma. JAMA Netw Open. 2023;6(11):e2342270 (Nov 8). doi: 10.1001/jamanetworkopen.2023.42270

Key clinical point: Premenopausal women with invasive lobular carcinoma (ILC) vs invasive ductal carcinoma (IDC) had better breast cancer-specific survival (BCSS) outcomes within 10 years after disease diagnosis, but the prognosis worsened in the long run.

Major finding: In the Surveillance, Epidemiology, and End Results (SEER) database, patients with ILC vs IDC showed improved BCSS outcomes during the first 10 years after diagnosis (hazard ratio [HR] 0.73; P < .001); however, after 10 years, the trend reversed and BCSS outcomes worsened by 80% in patients with ILC (HR 1.80; P < .001). ILC was also associated with worsened long-term prognosis in patients from the Korean Breast Cancer Registry and Asan Medical Center Research database.

Study details: This retrospective cohort study analyzed the data from three databases and included 225,938 premenopausal women (age < 50 years) with stages I-III ILC or IDC.

Disclosures: This study was supported by a grant from the Korea Health Technology R&D Project. O Metzger declared receiving grant funding and personal fees from various sources.

Source: Yoon TI et al. Survival outcomes in premenopausal patients with invasive lobular carcinoma. JAMA Netw Open. 2023;6(11):e2342270 (Nov 8). doi: 10.1001/jamanetworkopen.2023.42270

Key clinical point: Vaginal estrogen therapy did not worsen mortality outcomes in patients with breast cancer (BC) and genitourinary symptoms and can be considered if nonhormonal treatments prove unsuccessful.

Major finding: BC-specific mortality was not worsened in patients with BC who received vaginal estrogen therapy vs no hormone replacement therapy (hazard ratio 0.77; 95% CI 0.63-0.94).

Study details: Findings are from an analysis of two large cohorts including 49,237 females with BC, of which 5% of females used vaginal estrogen therapy after BC diagnosis.

Disclosures: This study was supported by grants from Cancer Research UK. Some authors declared receiving grants, personal fees, or nonfinancial support from and having other ties with several sources.

Source: McVicker L et al. Vaginal estrogen therapy use and survival in females with breast cancer. JAMA Oncol. 2023 (Nov 2). doi: 10.1001/jamaoncol.2023.4508

Key clinical point: Vaginal estrogen therapy did not worsen mortality outcomes in patients with breast cancer (BC) and genitourinary symptoms and can be considered if nonhormonal treatments prove unsuccessful.

Major finding: BC-specific mortality was not worsened in patients with BC who received vaginal estrogen therapy vs no hormone replacement therapy (hazard ratio 0.77; 95% CI 0.63-0.94).

Study details: Findings are from an analysis of two large cohorts including 49,237 females with BC, of which 5% of females used vaginal estrogen therapy after BC diagnosis.

Disclosures: This study was supported by grants from Cancer Research UK. Some authors declared receiving grants, personal fees, or nonfinancial support from and having other ties with several sources.

Source: McVicker L et al. Vaginal estrogen therapy use and survival in females with breast cancer. JAMA Oncol. 2023 (Nov 2). doi: 10.1001/jamaoncol.2023.4508

Key clinical point: Vaginal estrogen therapy did not worsen mortality outcomes in patients with breast cancer (BC) and genitourinary symptoms and can be considered if nonhormonal treatments prove unsuccessful.

Major finding: BC-specific mortality was not worsened in patients with BC who received vaginal estrogen therapy vs no hormone replacement therapy (hazard ratio 0.77; 95% CI 0.63-0.94).

Study details: Findings are from an analysis of two large cohorts including 49,237 females with BC, of which 5% of females used vaginal estrogen therapy after BC diagnosis.

Disclosures: This study was supported by grants from Cancer Research UK. Some authors declared receiving grants, personal fees, or nonfinancial support from and having other ties with several sources.

Source: McVicker L et al. Vaginal estrogen therapy use and survival in females with breast cancer. JAMA Oncol. 2023 (Nov 2). doi: 10.1001/jamaoncol.2023.4508

Developments in early breast cancer reported at the European Society for Medical Oncology (ESMO) 2023 Congress are discussed by Dr Lisa Carey of University of North Carolina, Chapel Hill. 

Dr Carey begins with 5-year results from the KEYNOTE-522 study in patients with early triple-negative breast cancer in which the immune checkpoint inhibitor pembrolizumab was incorporated into combination therapy both pre- and postoperatively. The new findings were consistent with earlier results, showing that pembrolizumab improved pathologic complete response (pCR) and event-free survival. 

Turning to human epidermal growth factor receptor 2–positive (HER2+) disease, Dr Carey discusses the PHERGain trial's use of a genomic assay to define risk and predict pCR. She suggests that such assays could lead to tailored therapy for HER2+ patients. 

On estrogen receptor–positive (ER+)/HER2- disease, Dr Carey reports first on KEYNOTE-756, which examined the addition of pembrolizumab to combination therapy for high-risk patients in both the neoadjuvant and adjuvant settings. Pembrolizumab improved pCR compared with placebo. 

Dr Carey closes by discussing another study in high-risk ER+/HER2- disease. Similar in design to KEYNOTE-756, CheckMate 7FL found that nivolumab added to combination therapy again augmented pCR results. 

--

Lisa A. Carey, MD, Distinguished Professor or Breast Cancer Research, University of North Carolina Lineberger Comprehensive Cancer Center; Professor, Division of Medical Oncology, Bassnight North Carolina Cancer Hospital, Chapel Hill, North Carolina  

Lisa A. Carey, MD, has disclosed no relevant financial relationships.

Developments in early breast cancer reported at the European Society for Medical Oncology (ESMO) 2023 Congress are discussed by Dr Lisa Carey of University of North Carolina, Chapel Hill. 

Dr Carey begins with 5-year results from the KEYNOTE-522 study in patients with early triple-negative breast cancer in which the immune checkpoint inhibitor pembrolizumab was incorporated into combination therapy both pre- and postoperatively. The new findings were consistent with earlier results, showing that pembrolizumab improved pathologic complete response (pCR) and event-free survival. 

Turning to human epidermal growth factor receptor 2–positive (HER2+) disease, Dr Carey discusses the PHERGain trial's use of a genomic assay to define risk and predict pCR. She suggests that such assays could lead to tailored therapy for HER2+ patients. 

On estrogen receptor–positive (ER+)/HER2- disease, Dr Carey reports first on KEYNOTE-756, which examined the addition of pembrolizumab to combination therapy for high-risk patients in both the neoadjuvant and adjuvant settings. Pembrolizumab improved pCR compared with placebo. 

Dr Carey closes by discussing another study in high-risk ER+/HER2- disease. Similar in design to KEYNOTE-756, CheckMate 7FL found that nivolumab added to combination therapy again augmented pCR results. 

--

Lisa A. Carey, MD, Distinguished Professor or Breast Cancer Research, University of North Carolina Lineberger Comprehensive Cancer Center; Professor, Division of Medical Oncology, Bassnight North Carolina Cancer Hospital, Chapel Hill, North Carolina  

Lisa A. Carey, MD, has disclosed no relevant financial relationships.

Developments in early breast cancer reported at the European Society for Medical Oncology (ESMO) 2023 Congress are discussed by Dr Lisa Carey of University of North Carolina, Chapel Hill. 

Dr Carey begins with 5-year results from the KEYNOTE-522 study in patients with early triple-negative breast cancer in which the immune checkpoint inhibitor pembrolizumab was incorporated into combination therapy both pre- and postoperatively. The new findings were consistent with earlier results, showing that pembrolizumab improved pathologic complete response (pCR) and event-free survival. 

Turning to human epidermal growth factor receptor 2–positive (HER2+) disease, Dr Carey discusses the PHERGain trial's use of a genomic assay to define risk and predict pCR. She suggests that such assays could lead to tailored therapy for HER2+ patients. 

On estrogen receptor–positive (ER+)/HER2- disease, Dr Carey reports first on KEYNOTE-756, which examined the addition of pembrolizumab to combination therapy for high-risk patients in both the neoadjuvant and adjuvant settings. Pembrolizumab improved pCR compared with placebo. 

Dr Carey closes by discussing another study in high-risk ER+/HER2- disease. Similar in design to KEYNOTE-756, CheckMate 7FL found that nivolumab added to combination therapy again augmented pCR results. 

--

Lisa A. Carey, MD, Distinguished Professor or Breast Cancer Research, University of North Carolina Lineberger Comprehensive Cancer Center; Professor, Division of Medical Oncology, Bassnight North Carolina Cancer Hospital, Chapel Hill, North Carolina  

Lisa A. Carey, MD, has disclosed no relevant financial relationships.

Angiosarcomas are uncommon, high-grade malignant tumors of endothelial cell origin that can arise via the lymphatics or vasculature. They typically occur spontaneously; however, there have been cases reported of benign vascular transformation. These tumors are more commonly found in elderly men on the head and neck in sun-damaged skin. Radiation-induced angiosarcoma occurs in an estimated 0.05%-0.3% of patients with breast cancer who underwent surgery and radiation therapy. This is a late complication, typically occurring about 5-10 years after radiation. Stewart-Treves syndrome, chronic lymphedema occurring after breast cancer treatment with axillary node dissection, increases the risk of angiosarcoma. As a vascular tumor, angiosarcoma spreads hematogenously and carries a poor prognosis if not caught early. Differential diagnoses include other vascular tumors such as retiform hemangioendothelioma. In this specific patient, the differential diagnosis includes Paget’s disease, chronic radiation skin changes, and eczema.

Histopathologically, angiosarcomas exhibit abnormal, pleomorphic, malignant endothelial cells. As the tumor progresses, the cell architecture becomes more distorted and cells form layers with papillary projections into the vascular lumen. Malignant cells may stain positive for CD31, CD34, the oncogene ERG and the proto-oncogene FLI-1. Histology in this patient revealed radiation changes in the dermis, as well as few vascular channels lined by large endothelial cells with marked nuclear atypia, in the form of large nucleoli and variably coarse chromatin. The cells were positive for MYC.

Treatment of angiosarcoma involves a multidisciplinary approach. Resection with wide margins is generally the treatment of choice. However, recurrence is relatively common, which may be a result of microsatellite deposits of the tumor. Perioperative radiation is recommended, and adjuvant chemotherapy often is recommended for metastatic disease. Specifically, paclitaxel has been found to promote survival in some cases of cutaneous angiosarcoma. Metastatic disease may be treated with cytotoxic drugs such as anthracyclines and taxanes. Additionally, targeted therapy including anti-VEGF drugs and tyrosine kinase inhibitors have been tested.

The case and photo were submitted by Mr. Shapiro of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Fla., and Dr. Bilu Martin. The column was edited by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Cohen-Hallaleh RB et al. Clin Sarcoma Res. 2017 Aug 7:7:15.

Cozzi S et al. Rep Pract Oncol Radiother. 2021 Sep 30;26(5):827-32.

Spiker AM, Mangla A, Ramsey ML. Angiosarcoma. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing; 2023 Jan-. Available from: www.ncbi.nlm.nih.gov/books/NBK441983/

Angiosarcomas are uncommon, high-grade malignant tumors of endothelial cell origin that can arise via the lymphatics or vasculature. They typically occur spontaneously; however, there have been cases reported of benign vascular transformation. These tumors are more commonly found in elderly men on the head and neck in sun-damaged skin. Radiation-induced angiosarcoma occurs in an estimated 0.05%-0.3% of patients with breast cancer who underwent surgery and radiation therapy. This is a late complication, typically occurring about 5-10 years after radiation. Stewart-Treves syndrome, chronic lymphedema occurring after breast cancer treatment with axillary node dissection, increases the risk of angiosarcoma. As a vascular tumor, angiosarcoma spreads hematogenously and carries a poor prognosis if not caught early. Differential diagnoses include other vascular tumors such as retiform hemangioendothelioma. In this specific patient, the differential diagnosis includes Paget’s disease, chronic radiation skin changes, and eczema.

Histopathologically, angiosarcomas exhibit abnormal, pleomorphic, malignant endothelial cells. As the tumor progresses, the cell architecture becomes more distorted and cells form layers with papillary projections into the vascular lumen. Malignant cells may stain positive for CD31, CD34, the oncogene ERG and the proto-oncogene FLI-1. Histology in this patient revealed radiation changes in the dermis, as well as few vascular channels lined by large endothelial cells with marked nuclear atypia, in the form of large nucleoli and variably coarse chromatin. The cells were positive for MYC.

Treatment of angiosarcoma involves a multidisciplinary approach. Resection with wide margins is generally the treatment of choice. However, recurrence is relatively common, which may be a result of microsatellite deposits of the tumor. Perioperative radiation is recommended, and adjuvant chemotherapy often is recommended for metastatic disease. Specifically, paclitaxel has been found to promote survival in some cases of cutaneous angiosarcoma. Metastatic disease may be treated with cytotoxic drugs such as anthracyclines and taxanes. Additionally, targeted therapy including anti-VEGF drugs and tyrosine kinase inhibitors have been tested.

The case and photo were submitted by Mr. Shapiro of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Fla., and Dr. Bilu Martin. The column was edited by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Cohen-Hallaleh RB et al. Clin Sarcoma Res. 2017 Aug 7:7:15.

Cozzi S et al. Rep Pract Oncol Radiother. 2021 Sep 30;26(5):827-32.

Spiker AM, Mangla A, Ramsey ML. Angiosarcoma. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing; 2023 Jan-. Available from: www.ncbi.nlm.nih.gov/books/NBK441983/

Angiosarcomas are uncommon, high-grade malignant tumors of endothelial cell origin that can arise via the lymphatics or vasculature. They typically occur spontaneously; however, there have been cases reported of benign vascular transformation. These tumors are more commonly found in elderly men on the head and neck in sun-damaged skin. Radiation-induced angiosarcoma occurs in an estimated 0.05%-0.3% of patients with breast cancer who underwent surgery and radiation therapy. This is a late complication, typically occurring about 5-10 years after radiation. Stewart-Treves syndrome, chronic lymphedema occurring after breast cancer treatment with axillary node dissection, increases the risk of angiosarcoma. As a vascular tumor, angiosarcoma spreads hematogenously and carries a poor prognosis if not caught early. Differential diagnoses include other vascular tumors such as retiform hemangioendothelioma. In this specific patient, the differential diagnosis includes Paget’s disease, chronic radiation skin changes, and eczema.

Histopathologically, angiosarcomas exhibit abnormal, pleomorphic, malignant endothelial cells. As the tumor progresses, the cell architecture becomes more distorted and cells form layers with papillary projections into the vascular lumen. Malignant cells may stain positive for CD31, CD34, the oncogene ERG and the proto-oncogene FLI-1. Histology in this patient revealed radiation changes in the dermis, as well as few vascular channels lined by large endothelial cells with marked nuclear atypia, in the form of large nucleoli and variably coarse chromatin. The cells were positive for MYC.

Treatment of angiosarcoma involves a multidisciplinary approach. Resection with wide margins is generally the treatment of choice. However, recurrence is relatively common, which may be a result of microsatellite deposits of the tumor. Perioperative radiation is recommended, and adjuvant chemotherapy often is recommended for metastatic disease. Specifically, paclitaxel has been found to promote survival in some cases of cutaneous angiosarcoma. Metastatic disease may be treated with cytotoxic drugs such as anthracyclines and taxanes. Additionally, targeted therapy including anti-VEGF drugs and tyrosine kinase inhibitors have been tested.

The case and photo were submitted by Mr. Shapiro of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Fla., and Dr. Bilu Martin. The column was edited by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Cohen-Hallaleh RB et al. Clin Sarcoma Res. 2017 Aug 7:7:15.

Cozzi S et al. Rep Pract Oncol Radiother. 2021 Sep 30;26(5):827-32.

Spiker AM, Mangla A, Ramsey ML. Angiosarcoma. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing; 2023 Jan-. Available from: www.ncbi.nlm.nih.gov/books/NBK441983/

MADRID – Fine particulate matter pollution in the atmosphere around homes and workplaces increases the risk for breast cancer, according to a new analysis of the XENAIR study presented at the European Society of Medical Oncology (ESMO) Congress 2023. Béatrice Fervers, MD, PhD, head of the environmental cancer prevention department at the Léon Bérard Center, Lyon, France, presented her findings.

“To our knowledge, this study is the first to examine the risk of breast cancer associated with long-term exposure of subjects to atmospheric pollution both at home and in the workplace, estimated using a very small spatial resolution [statistical] model,” said the researchers.

“Our data showed a statistically significant association between long-term exposure to fine particulate matter air pollution, at home and at work, and risk of breast cancer. This [finding] contrasts with previous research that looked only at fine particulate exposure where women were living and showed small or no effects on breast cancer risk,” said Dr. Fervers in a press release issued before the Congress.

The XENAIR study carried out on the prospective, longitudinal E3N cohort a year ago showed an increased risk for breast cancer after exposure to five atmospheric pollutants. Notably, it showed an increased risk in women exposed to BaP and PCB153, two pollutants classed as endocrine-disrupting chemicals, during perimenopause.
 

Increased linear risk

In this new analysis, exposure to PM2.5, PM10, and NO2 pollution at home and in the workplace of 2,419 women with breast cancer was compared with that of 2,984 women without breast cancer during the period from 1990 to 2011.

This was a case-control study in which participants were matched by department of residence in France, age (± 1 year), date (± 3 months), and menopausal status at the time of the blood draw.

Breast cancer risk increased by 28% when exposure to fine particulate (PM2.5) air pollution increased by 10 mcg/m3. The increment is approximately equivalent to the difference in PM2.5 particulate concentration typically seen in rural versus urban areas of Europe.

Smaller increases in breast cancer risk were also recorded in women exposed to high levels of larger particulate air pollution (PM10 and NO2).

No change in effect was seen according to menopausal status. Analyses that examined hormone receptor status showed a positive but not significant association for PM2.5 in cases of estrogen receptor positive breast cancer.

Dr. Fervers and colleagues plan to investigate the effects of pollution exposure during the commute to get a complete picture of effects on breast cancer risk.
 

Regulators respond

Charles Swanton, PhD, a clinician scientist at the Francis Crick Institute, London, emphasized the importance of these new results for breast cancer. At last year’s ESMO Congress, he explained how particulate matter air pollution caused tumor proliferation in patients with a certain type of genetic mutation.

“Fine particle pollutants can penetrate deep into the lungs, enter the bloodstream, and be absorbed into breast and other tissue. There is already evidence that air pollutants can change the architecture of the breast. It will be important to test if pollutants allow cells in breast tissue with pre-existing mutations to expand and drive tumor promotion, possibly through inflammatory processes, similar to our observations in nonsmokers with lung cancer,” said Dr. Swanton in the ESMO press release.

“It is very concerning that small pollutant particles in the air and indeed microplastic particles of similar size are getting into the environment when we don’t yet understand their potential to promote cancer. There is an urgent need to set up laboratory studies to investigate the effects of these small air pollutant particles on the latency, grade, aggression, and progression of breast tumors,” he added.

“There is now strong epidemiological and biological evidence for the link between PM2.5 particulate exposure and cancer, and there are good clinical and economic reasons for reducing pollution to prevent cancers,” said Jean-Yves Blay, MD, PhD, director of public policy for ESMO.

Following a proposal from the European Commission in October 2022 to reduce the limit for PM2.5 particulates in the air from the current 25 mcg/m3 to 10 mcg/m3 by 2030, ESMO urged a further reduction in the PM2.5 limit to 5 mcg/m3, in line with the World Health Organization’s air quality guidance, according to the press release.

“Reducing PM2.5 particles in the air to the WHO recommended level is critical because of their association with a variety of tumor types, including breast cancer,” Dr. Blay added.

In September 2023, the European Parliament adopted in a plenary session its report on the ongoing revision of the EU Ambient Air Quality Directives, which reflects ESMO’s recommendations to set the annual limit value for PM2.5 at 5 mcg/m³. This adoption opens interinstitutional negotiations between the legislators (the European Parliament, European Commission, and EU Council) to agree on the final text of the directive.

“By supporting our requests with solid scientific evidence, we are offering a new dimension to health public policy. The work is not over, and change will not happen overnight, but we are moving in the right direction,” concluded Dr. Blay.

The new analysis of the XENAIR study was funded by ARC Foundation for cancer research; the French Agency for Food, Environmental, and Occupational Health and Safety; French National League against Cancer; and Fondation de France, an independent private organization, recognized as being in the public interest. The authors report no relevant financial relationships.

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

MADRID – Fine particulate matter pollution in the atmosphere around homes and workplaces increases the risk for breast cancer, according to a new analysis of the XENAIR study presented at the European Society of Medical Oncology (ESMO) Congress 2023. Béatrice Fervers, MD, PhD, head of the environmental cancer prevention department at the Léon Bérard Center, Lyon, France, presented her findings.

“To our knowledge, this study is the first to examine the risk of breast cancer associated with long-term exposure of subjects to atmospheric pollution both at home and in the workplace, estimated using a very small spatial resolution [statistical] model,” said the researchers.

“Our data showed a statistically significant association between long-term exposure to fine particulate matter air pollution, at home and at work, and risk of breast cancer. This [finding] contrasts with previous research that looked only at fine particulate exposure where women were living and showed small or no effects on breast cancer risk,” said Dr. Fervers in a press release issued before the Congress.

The XENAIR study carried out on the prospective, longitudinal E3N cohort a year ago showed an increased risk for breast cancer after exposure to five atmospheric pollutants. Notably, it showed an increased risk in women exposed to BaP and PCB153, two pollutants classed as endocrine-disrupting chemicals, during perimenopause.
 

Increased linear risk

In this new analysis, exposure to PM2.5, PM10, and NO2 pollution at home and in the workplace of 2,419 women with breast cancer was compared with that of 2,984 women without breast cancer during the period from 1990 to 2011.

This was a case-control study in which participants were matched by department of residence in France, age (± 1 year), date (± 3 months), and menopausal status at the time of the blood draw.

Breast cancer risk increased by 28% when exposure to fine particulate (PM2.5) air pollution increased by 10 mcg/m3. The increment is approximately equivalent to the difference in PM2.5 particulate concentration typically seen in rural versus urban areas of Europe.

Smaller increases in breast cancer risk were also recorded in women exposed to high levels of larger particulate air pollution (PM10 and NO2).

No change in effect was seen according to menopausal status. Analyses that examined hormone receptor status showed a positive but not significant association for PM2.5 in cases of estrogen receptor positive breast cancer.

Dr. Fervers and colleagues plan to investigate the effects of pollution exposure during the commute to get a complete picture of effects on breast cancer risk.
 

Regulators respond

Charles Swanton, PhD, a clinician scientist at the Francis Crick Institute, London, emphasized the importance of these new results for breast cancer. At last year’s ESMO Congress, he explained how particulate matter air pollution caused tumor proliferation in patients with a certain type of genetic mutation.

“Fine particle pollutants can penetrate deep into the lungs, enter the bloodstream, and be absorbed into breast and other tissue. There is already evidence that air pollutants can change the architecture of the breast. It will be important to test if pollutants allow cells in breast tissue with pre-existing mutations to expand and drive tumor promotion, possibly through inflammatory processes, similar to our observations in nonsmokers with lung cancer,” said Dr. Swanton in the ESMO press release.

“It is very concerning that small pollutant particles in the air and indeed microplastic particles of similar size are getting into the environment when we don’t yet understand their potential to promote cancer. There is an urgent need to set up laboratory studies to investigate the effects of these small air pollutant particles on the latency, grade, aggression, and progression of breast tumors,” he added.

“There is now strong epidemiological and biological evidence for the link between PM2.5 particulate exposure and cancer, and there are good clinical and economic reasons for reducing pollution to prevent cancers,” said Jean-Yves Blay, MD, PhD, director of public policy for ESMO.

Following a proposal from the European Commission in October 2022 to reduce the limit for PM2.5 particulates in the air from the current 25 mcg/m3 to 10 mcg/m3 by 2030, ESMO urged a further reduction in the PM2.5 limit to 5 mcg/m3, in line with the World Health Organization’s air quality guidance, according to the press release.

“Reducing PM2.5 particles in the air to the WHO recommended level is critical because of their association with a variety of tumor types, including breast cancer,” Dr. Blay added.

In September 2023, the European Parliament adopted in a plenary session its report on the ongoing revision of the EU Ambient Air Quality Directives, which reflects ESMO’s recommendations to set the annual limit value for PM2.5 at 5 mcg/m³. This adoption opens interinstitutional negotiations between the legislators (the European Parliament, European Commission, and EU Council) to agree on the final text of the directive.

“By supporting our requests with solid scientific evidence, we are offering a new dimension to health public policy. The work is not over, and change will not happen overnight, but we are moving in the right direction,” concluded Dr. Blay.

The new analysis of the XENAIR study was funded by ARC Foundation for cancer research; the French Agency for Food, Environmental, and Occupational Health and Safety; French National League against Cancer; and Fondation de France, an independent private organization, recognized as being in the public interest. The authors report no relevant financial relationships.

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

MADRID – Fine particulate matter pollution in the atmosphere around homes and workplaces increases the risk for breast cancer, according to a new analysis of the XENAIR study presented at the European Society of Medical Oncology (ESMO) Congress 2023. Béatrice Fervers, MD, PhD, head of the environmental cancer prevention department at the Léon Bérard Center, Lyon, France, presented her findings.

“To our knowledge, this study is the first to examine the risk of breast cancer associated with long-term exposure of subjects to atmospheric pollution both at home and in the workplace, estimated using a very small spatial resolution [statistical] model,” said the researchers.

“Our data showed a statistically significant association between long-term exposure to fine particulate matter air pollution, at home and at work, and risk of breast cancer. This [finding] contrasts with previous research that looked only at fine particulate exposure where women were living and showed small or no effects on breast cancer risk,” said Dr. Fervers in a press release issued before the Congress.

The XENAIR study carried out on the prospective, longitudinal E3N cohort a year ago showed an increased risk for breast cancer after exposure to five atmospheric pollutants. Notably, it showed an increased risk in women exposed to BaP and PCB153, two pollutants classed as endocrine-disrupting chemicals, during perimenopause.
 

Increased linear risk

In this new analysis, exposure to PM2.5, PM10, and NO2 pollution at home and in the workplace of 2,419 women with breast cancer was compared with that of 2,984 women without breast cancer during the period from 1990 to 2011.

This was a case-control study in which participants were matched by department of residence in France, age (± 1 year), date (± 3 months), and menopausal status at the time of the blood draw.

Breast cancer risk increased by 28% when exposure to fine particulate (PM2.5) air pollution increased by 10 mcg/m3. The increment is approximately equivalent to the difference in PM2.5 particulate concentration typically seen in rural versus urban areas of Europe.

Smaller increases in breast cancer risk were also recorded in women exposed to high levels of larger particulate air pollution (PM10 and NO2).

No change in effect was seen according to menopausal status. Analyses that examined hormone receptor status showed a positive but not significant association for PM2.5 in cases of estrogen receptor positive breast cancer.

Dr. Fervers and colleagues plan to investigate the effects of pollution exposure during the commute to get a complete picture of effects on breast cancer risk.
 

Regulators respond

Charles Swanton, PhD, a clinician scientist at the Francis Crick Institute, London, emphasized the importance of these new results for breast cancer. At last year’s ESMO Congress, he explained how particulate matter air pollution caused tumor proliferation in patients with a certain type of genetic mutation.

“Fine particle pollutants can penetrate deep into the lungs, enter the bloodstream, and be absorbed into breast and other tissue. There is already evidence that air pollutants can change the architecture of the breast. It will be important to test if pollutants allow cells in breast tissue with pre-existing mutations to expand and drive tumor promotion, possibly through inflammatory processes, similar to our observations in nonsmokers with lung cancer,” said Dr. Swanton in the ESMO press release.

“It is very concerning that small pollutant particles in the air and indeed microplastic particles of similar size are getting into the environment when we don’t yet understand their potential to promote cancer. There is an urgent need to set up laboratory studies to investigate the effects of these small air pollutant particles on the latency, grade, aggression, and progression of breast tumors,” he added.

“There is now strong epidemiological and biological evidence for the link between PM2.5 particulate exposure and cancer, and there are good clinical and economic reasons for reducing pollution to prevent cancers,” said Jean-Yves Blay, MD, PhD, director of public policy for ESMO.

Following a proposal from the European Commission in October 2022 to reduce the limit for PM2.5 particulates in the air from the current 25 mcg/m3 to 10 mcg/m3 by 2030, ESMO urged a further reduction in the PM2.5 limit to 5 mcg/m3, in line with the World Health Organization’s air quality guidance, according to the press release.

“Reducing PM2.5 particles in the air to the WHO recommended level is critical because of their association with a variety of tumor types, including breast cancer,” Dr. Blay added.

In September 2023, the European Parliament adopted in a plenary session its report on the ongoing revision of the EU Ambient Air Quality Directives, which reflects ESMO’s recommendations to set the annual limit value for PM2.5 at 5 mcg/m³. This adoption opens interinstitutional negotiations between the legislators (the European Parliament, European Commission, and EU Council) to agree on the final text of the directive.

“By supporting our requests with solid scientific evidence, we are offering a new dimension to health public policy. The work is not over, and change will not happen overnight, but we are moving in the right direction,” concluded Dr. Blay.

The new analysis of the XENAIR study was funded by ARC Foundation for cancer research; the French Agency for Food, Environmental, and Occupational Health and Safety; French National League against Cancer; and Fondation de France, an independent private organization, recognized as being in the public interest. The authors report no relevant financial relationships.

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

TOPLINE:

Patients with breast cancer who have low levels of vitamin D when they begin treatment with paclitaxel are more likely to develop peripheral neuropathy, suggesting that correcting levels before treatment might help prevent the condition.

METHODOLOGY:

• Past studies have suggested an association between vitamin D insufficiency and paclitaxel-induced peripheral neuropathy, a largely untreatable and sometimes permanent side effect of chemotherapy.
• To confirm the association, investigators reviewed data and samples from 1,191 women in the phase 3 SWOG S0221 trial, which compared weekly and biweekly paclitaxel regimens for early-stage breast cancer.
• Using serum samples collected at baseline, the team evaluated the relationship between insufficient vitamin D levels (20 ng/mL or less) before treatment and grade 3 or higher sensory chemotherapy-induced peripheral neuropathy.

TAKEAWAY:

• Overall, 33.3% of the women had insufficient vitamin D levels at baseline, and 16.4% developed grade 3 or worse sensory chemotherapy-induced peripheral neuropathy.
• The incidence of peripheral neuropathy of grade 3 or greater was higher among patients with pretreatment vitamin D insufficiency (20.7% vs. 14.2%; odds ratio, 1.57; P = .005).
• The association grew stronger after adjusting for age and paclitaxel schedule (adjusted OR, 1.65; P = .003), but not after adjusting for race (adjusted OR, 1.39; P = .066).

IN PRACTICE:

The study “confirms that patients with pretreatment vitamin D insufficiency have a higher incidence of [chemotherapy-induced peripheral neuropathy],” the authors concluded. These results also “suggest that vitamin D supplementation in patients with lower levels of vitamin D may reduce peripheral neuropathy, and particularly high-grade peripheral neuropathy, which would improve these patients’ long-term quality of life,” senior researcher Daniel L. Hertz, PharmD, PhD, University of Michigan College of Pharmacy, Ann Arbor, said in a press release.

SOURCE:

The study, led by Ciao-Sin Chen, PharmD, of the University of Michigan, Ann Arbor, was published in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The trial did not collect data on other peripheral neuropathy risk factors, including preexisting peripheral neuropathy and diabetes. The study included a limited number of non-White participants (16%); larger numbers are needed to elucidate a potential interplay between race, vitamin D, and chemotherapy-induced peripheral neuropathy. The researchers also did not collect data on grade 1 and 2 chemotherapy-induced peripheral neuropathy.

DISCLOSURES:

The study was funded by Amgen, the American Cancer Society, and others. The investigators disclosed no relevant financial relationships.

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

TOPLINE:

Patients with breast cancer who have low levels of vitamin D when they begin treatment with paclitaxel are more likely to develop peripheral neuropathy, suggesting that correcting levels before treatment might help prevent the condition.

METHODOLOGY:

• Past studies have suggested an association between vitamin D insufficiency and paclitaxel-induced peripheral neuropathy, a largely untreatable and sometimes permanent side effect of chemotherapy.
• To confirm the association, investigators reviewed data and samples from 1,191 women in the phase 3 SWOG S0221 trial, which compared weekly and biweekly paclitaxel regimens for early-stage breast cancer.
• Using serum samples collected at baseline, the team evaluated the relationship between insufficient vitamin D levels (20 ng/mL or less) before treatment and grade 3 or higher sensory chemotherapy-induced peripheral neuropathy.

TAKEAWAY:

• Overall, 33.3% of the women had insufficient vitamin D levels at baseline, and 16.4% developed grade 3 or worse sensory chemotherapy-induced peripheral neuropathy.
• The incidence of peripheral neuropathy of grade 3 or greater was higher among patients with pretreatment vitamin D insufficiency (20.7% vs. 14.2%; odds ratio, 1.57; P = .005).
• The association grew stronger after adjusting for age and paclitaxel schedule (adjusted OR, 1.65; P = .003), but not after adjusting for race (adjusted OR, 1.39; P = .066).

IN PRACTICE:

The study “confirms that patients with pretreatment vitamin D insufficiency have a higher incidence of [chemotherapy-induced peripheral neuropathy],” the authors concluded. These results also “suggest that vitamin D supplementation in patients with lower levels of vitamin D may reduce peripheral neuropathy, and particularly high-grade peripheral neuropathy, which would improve these patients’ long-term quality of life,” senior researcher Daniel L. Hertz, PharmD, PhD, University of Michigan College of Pharmacy, Ann Arbor, said in a press release.

SOURCE:

The study, led by Ciao-Sin Chen, PharmD, of the University of Michigan, Ann Arbor, was published in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The trial did not collect data on other peripheral neuropathy risk factors, including preexisting peripheral neuropathy and diabetes. The study included a limited number of non-White participants (16%); larger numbers are needed to elucidate a potential interplay between race, vitamin D, and chemotherapy-induced peripheral neuropathy. The researchers also did not collect data on grade 1 and 2 chemotherapy-induced peripheral neuropathy.

DISCLOSURES:

The study was funded by Amgen, the American Cancer Society, and others. The investigators disclosed no relevant financial relationships.

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

TOPLINE:

Patients with breast cancer who have low levels of vitamin D when they begin treatment with paclitaxel are more likely to develop peripheral neuropathy, suggesting that correcting levels before treatment might help prevent the condition.

METHODOLOGY:

• Past studies have suggested an association between vitamin D insufficiency and paclitaxel-induced peripheral neuropathy, a largely untreatable and sometimes permanent side effect of chemotherapy.
• To confirm the association, investigators reviewed data and samples from 1,191 women in the phase 3 SWOG S0221 trial, which compared weekly and biweekly paclitaxel regimens for early-stage breast cancer.
• Using serum samples collected at baseline, the team evaluated the relationship between insufficient vitamin D levels (20 ng/mL or less) before treatment and grade 3 or higher sensory chemotherapy-induced peripheral neuropathy.

TAKEAWAY:

• Overall, 33.3% of the women had insufficient vitamin D levels at baseline, and 16.4% developed grade 3 or worse sensory chemotherapy-induced peripheral neuropathy.
• The incidence of peripheral neuropathy of grade 3 or greater was higher among patients with pretreatment vitamin D insufficiency (20.7% vs. 14.2%; odds ratio, 1.57; P = .005).
• The association grew stronger after adjusting for age and paclitaxel schedule (adjusted OR, 1.65; P = .003), but not after adjusting for race (adjusted OR, 1.39; P = .066).

IN PRACTICE:

The study “confirms that patients with pretreatment vitamin D insufficiency have a higher incidence of [chemotherapy-induced peripheral neuropathy],” the authors concluded. These results also “suggest that vitamin D supplementation in patients with lower levels of vitamin D may reduce peripheral neuropathy, and particularly high-grade peripheral neuropathy, which would improve these patients’ long-term quality of life,” senior researcher Daniel L. Hertz, PharmD, PhD, University of Michigan College of Pharmacy, Ann Arbor, said in a press release.

SOURCE:

The study, led by Ciao-Sin Chen, PharmD, of the University of Michigan, Ann Arbor, was published in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The trial did not collect data on other peripheral neuropathy risk factors, including preexisting peripheral neuropathy and diabetes. The study included a limited number of non-White participants (16%); larger numbers are needed to elucidate a potential interplay between race, vitamin D, and chemotherapy-induced peripheral neuropathy. The researchers also did not collect data on grade 1 and 2 chemotherapy-induced peripheral neuropathy.

DISCLOSURES:

The study was funded by Amgen, the American Cancer Society, and others. The investigators disclosed no relevant financial relationships.

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

Trastuzumab deruxtecan (T-DXd) provided sustained clinically meaningful improvement versus physician’s choice of treatment (TPC) for patients with advanced breast cancer and low HER2 expression in the randomized phase 3 DESTINY-Breast04 study, according to 32-month follow-up data.

The overall safety profile of the HER2-directed antibody drug conjugate was also comparable to that observed at the primary analysis in 2022, and longer exposure did not appear to increase toxicity, Shanu Modi, MD, reported on behalf of the DESTINY-Breast04 investigators at the European Society of Medical Oncology (ESMO) Congress 2023.

“These results continue to support the use of T-DXd as the new standard of care after one line of chemotherapy in patients with HER2-low metastatic breast cancer,” said Dr. Modi, a breast oncologist and attending physician at Memorial Sloan Kettering Cancer Center, New York.

DESTINY-Breast04 enrolled 557 patients 2:1 to receive 5.4 mg/kg of T-DXd every 3 weeks or physicians’ choice of capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel, and established HER2-low mBC as “a new targetable patient population with T-DXd as a new standard of care,” she explained.

Median overall survival (mOS) with a median of 18.4 months of follow-up at the Jan. 11, 2022, primary data cut-off was 23.4 months in the T-DXd arm versus 16.8 months in the TPC arm and 23.9 versus 17.5 months, respectively, in the hormone receptor–positive (HR+) cohort (hazard ratio, 0.64 for both groups). At the preplanned extended follow-up with data cut-off on March 1, 2023, the mOS was 22.9 versus 16.8 months for T-DXd versus TPC, and 23.9 versus 17.6 months for the HR+ cohort, respectively (HR, 0.69 for both).

Median progression-free survival (PFS) by investigator assessment was 8.8 versus 4.2 months for the full cohort, and 9.6 versus 4.2 months for the HR+ cohort (HR, 0.36 and 0.37, respectively). PFS was consistent with the results from the primary analysis.

The benefits in the HR+ patients were consistent across all patient subgroups, Dr. Modi noted.

“I do think it’s interesting to point out that at the landmark 2-year point, all patients on standard chemotherapy discontinued study treatment, whereas 15% on T-DXd remain [on treatment] without any evidence of disease progression, Dr. Modi added

An exploratory analysis in the hormone receptor–negative (HR–) cohort showed mOS of 18.2 versus 8.3 months at the primary analysis (HR, 0.48), and a “clinically meaningful and numerical advantage for T-DXd” persisted at the planned follow-up (mOS, 17.1 vs. 8.3; HR, 0.58), she said.

PFS in the HR- cohort was 8.5 versus 2.9 months at the primary analysis, and 6.3 versus 2.9 months at the update (HR, 0.46 and 0.29, respectively).

An assessment of post-study therapies received by patients showed that those therapies did not account for the significant survival advantage conferred by T-DXd, Dr. Modi said.

She noted, however, that while no new safety signals were observed at follow-up, lung toxicity remains a “toxicity of special interest,” having occurred in 12.1% of cases at the time of the primary analysis.

Most cases were grade 1 or 2, and no new cases were observed at follow-up, but one patient with lung toxicity and an initial grade 3 event experienced clinical deterioration and later died from lung toxicity, which underscores the importance of remaining vigilant and intervening promptly in all cases of lung toxicity, Dr. Modi stressed.

Invited discussant Giampaolo Bianchini, MD, reiterated that T-DXd is an effective treatment option and said, “we must accurately identify patients and avoid improperly denying this important therapeutic option.”

Although HER2-low disease is not a unique biological disease entity, it is a “practical and pragmatic definition used to select patients with ‘some degree’ of HER2 protein expression adopting a test and a scoring system already implemented in the routine clinical practice,” said Dr. Bianchini, head of the breast cancer group and head of clinical translational and immunotherapy research at IRCCS Ospedale, San Raffaele, Milan.

However, the current definition may be inadequate, he said, explaining that the ongoing DESTINY-Breast06 study “will challenge the current definition of what we consider HER2-low definition,” potentially extending the T-DXd indication to HER2 ultra-low.

Furthermore, current HER2 testing was designed to discriminate cases with high abundant protein – not for the low HER2 dynamic range, which leads to technical inaccuracy.

Given these considerations, he suggested considering a new biopsy, if feasible, in patients with an immunohistochemistry (IHC) score of 0 in all tumor biopsies, and having a revision performed by the pathologist.

In patients with an IHC score of 1 or greater only in one biopsy, there is no need to confirm the HER2-low status, he said.

DESTINY-Breast04 is funded by Daiichi Sankyo Inc. and AstraZeneca. Dr. Modi reported relationships with Daiichi Sankyo, Genentech, AstraZeneca, Seagen, and MacroGenics. Dr. Bianchini reported relationships with AstraZeneca, Daiichi Sankyo, Gilead, MSD, Seagen, Roche, Sanofi, Lilly, EISAI, Novartis, Pfizer, Stemline, Exact Science, and Agendia.

Trastuzumab deruxtecan (T-DXd) provided sustained clinically meaningful improvement versus physician’s choice of treatment (TPC) for patients with advanced breast cancer and low HER2 expression in the randomized phase 3 DESTINY-Breast04 study, according to 32-month follow-up data.

The overall safety profile of the HER2-directed antibody drug conjugate was also comparable to that observed at the primary analysis in 2022, and longer exposure did not appear to increase toxicity, Shanu Modi, MD, reported on behalf of the DESTINY-Breast04 investigators at the European Society of Medical Oncology (ESMO) Congress 2023.

“These results continue to support the use of T-DXd as the new standard of care after one line of chemotherapy in patients with HER2-low metastatic breast cancer,” said Dr. Modi, a breast oncologist and attending physician at Memorial Sloan Kettering Cancer Center, New York.

DESTINY-Breast04 enrolled 557 patients 2:1 to receive 5.4 mg/kg of T-DXd every 3 weeks or physicians’ choice of capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel, and established HER2-low mBC as “a new targetable patient population with T-DXd as a new standard of care,” she explained.

Median overall survival (mOS) with a median of 18.4 months of follow-up at the Jan. 11, 2022, primary data cut-off was 23.4 months in the T-DXd arm versus 16.8 months in the TPC arm and 23.9 versus 17.5 months, respectively, in the hormone receptor–positive (HR+) cohort (hazard ratio, 0.64 for both groups). At the preplanned extended follow-up with data cut-off on March 1, 2023, the mOS was 22.9 versus 16.8 months for T-DXd versus TPC, and 23.9 versus 17.6 months for the HR+ cohort, respectively (HR, 0.69 for both).

Median progression-free survival (PFS) by investigator assessment was 8.8 versus 4.2 months for the full cohort, and 9.6 versus 4.2 months for the HR+ cohort (HR, 0.36 and 0.37, respectively). PFS was consistent with the results from the primary analysis.

The benefits in the HR+ patients were consistent across all patient subgroups, Dr. Modi noted.

“I do think it’s interesting to point out that at the landmark 2-year point, all patients on standard chemotherapy discontinued study treatment, whereas 15% on T-DXd remain [on treatment] without any evidence of disease progression, Dr. Modi added

An exploratory analysis in the hormone receptor–negative (HR–) cohort showed mOS of 18.2 versus 8.3 months at the primary analysis (HR, 0.48), and a “clinically meaningful and numerical advantage for T-DXd” persisted at the planned follow-up (mOS, 17.1 vs. 8.3; HR, 0.58), she said.

PFS in the HR- cohort was 8.5 versus 2.9 months at the primary analysis, and 6.3 versus 2.9 months at the update (HR, 0.46 and 0.29, respectively).

An assessment of post-study therapies received by patients showed that those therapies did not account for the significant survival advantage conferred by T-DXd, Dr. Modi said.

She noted, however, that while no new safety signals were observed at follow-up, lung toxicity remains a “toxicity of special interest,” having occurred in 12.1% of cases at the time of the primary analysis.

Most cases were grade 1 or 2, and no new cases were observed at follow-up, but one patient with lung toxicity and an initial grade 3 event experienced clinical deterioration and later died from lung toxicity, which underscores the importance of remaining vigilant and intervening promptly in all cases of lung toxicity, Dr. Modi stressed.

Invited discussant Giampaolo Bianchini, MD, reiterated that T-DXd is an effective treatment option and said, “we must accurately identify patients and avoid improperly denying this important therapeutic option.”

Although HER2-low disease is not a unique biological disease entity, it is a “practical and pragmatic definition used to select patients with ‘some degree’ of HER2 protein expression adopting a test and a scoring system already implemented in the routine clinical practice,” said Dr. Bianchini, head of the breast cancer group and head of clinical translational and immunotherapy research at IRCCS Ospedale, San Raffaele, Milan.

However, the current definition may be inadequate, he said, explaining that the ongoing DESTINY-Breast06 study “will challenge the current definition of what we consider HER2-low definition,” potentially extending the T-DXd indication to HER2 ultra-low.

Furthermore, current HER2 testing was designed to discriminate cases with high abundant protein – not for the low HER2 dynamic range, which leads to technical inaccuracy.

Given these considerations, he suggested considering a new biopsy, if feasible, in patients with an immunohistochemistry (IHC) score of 0 in all tumor biopsies, and having a revision performed by the pathologist.

In patients with an IHC score of 1 or greater only in one biopsy, there is no need to confirm the HER2-low status, he said.

DESTINY-Breast04 is funded by Daiichi Sankyo Inc. and AstraZeneca. Dr. Modi reported relationships with Daiichi Sankyo, Genentech, AstraZeneca, Seagen, and MacroGenics. Dr. Bianchini reported relationships with AstraZeneca, Daiichi Sankyo, Gilead, MSD, Seagen, Roche, Sanofi, Lilly, EISAI, Novartis, Pfizer, Stemline, Exact Science, and Agendia.

Trastuzumab deruxtecan (T-DXd) provided sustained clinically meaningful improvement versus physician’s choice of treatment (TPC) for patients with advanced breast cancer and low HER2 expression in the randomized phase 3 DESTINY-Breast04 study, according to 32-month follow-up data.

The overall safety profile of the HER2-directed antibody drug conjugate was also comparable to that observed at the primary analysis in 2022, and longer exposure did not appear to increase toxicity, Shanu Modi, MD, reported on behalf of the DESTINY-Breast04 investigators at the European Society of Medical Oncology (ESMO) Congress 2023.

“These results continue to support the use of T-DXd as the new standard of care after one line of chemotherapy in patients with HER2-low metastatic breast cancer,” said Dr. Modi, a breast oncologist and attending physician at Memorial Sloan Kettering Cancer Center, New York.

DESTINY-Breast04 enrolled 557 patients 2:1 to receive 5.4 mg/kg of T-DXd every 3 weeks or physicians’ choice of capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel, and established HER2-low mBC as “a new targetable patient population with T-DXd as a new standard of care,” she explained.

Median overall survival (mOS) with a median of 18.4 months of follow-up at the Jan. 11, 2022, primary data cut-off was 23.4 months in the T-DXd arm versus 16.8 months in the TPC arm and 23.9 versus 17.5 months, respectively, in the hormone receptor–positive (HR+) cohort (hazard ratio, 0.64 for both groups). At the preplanned extended follow-up with data cut-off on March 1, 2023, the mOS was 22.9 versus 16.8 months for T-DXd versus TPC, and 23.9 versus 17.6 months for the HR+ cohort, respectively (HR, 0.69 for both).

Median progression-free survival (PFS) by investigator assessment was 8.8 versus 4.2 months for the full cohort, and 9.6 versus 4.2 months for the HR+ cohort (HR, 0.36 and 0.37, respectively). PFS was consistent with the results from the primary analysis.

The benefits in the HR+ patients were consistent across all patient subgroups, Dr. Modi noted.

“I do think it’s interesting to point out that at the landmark 2-year point, all patients on standard chemotherapy discontinued study treatment, whereas 15% on T-DXd remain [on treatment] without any evidence of disease progression, Dr. Modi added

An exploratory analysis in the hormone receptor–negative (HR–) cohort showed mOS of 18.2 versus 8.3 months at the primary analysis (HR, 0.48), and a “clinically meaningful and numerical advantage for T-DXd” persisted at the planned follow-up (mOS, 17.1 vs. 8.3; HR, 0.58), she said.

PFS in the HR- cohort was 8.5 versus 2.9 months at the primary analysis, and 6.3 versus 2.9 months at the update (HR, 0.46 and 0.29, respectively).

An assessment of post-study therapies received by patients showed that those therapies did not account for the significant survival advantage conferred by T-DXd, Dr. Modi said.

She noted, however, that while no new safety signals were observed at follow-up, lung toxicity remains a “toxicity of special interest,” having occurred in 12.1% of cases at the time of the primary analysis.

Most cases were grade 1 or 2, and no new cases were observed at follow-up, but one patient with lung toxicity and an initial grade 3 event experienced clinical deterioration and later died from lung toxicity, which underscores the importance of remaining vigilant and intervening promptly in all cases of lung toxicity, Dr. Modi stressed.

Invited discussant Giampaolo Bianchini, MD, reiterated that T-DXd is an effective treatment option and said, “we must accurately identify patients and avoid improperly denying this important therapeutic option.”

Although HER2-low disease is not a unique biological disease entity, it is a “practical and pragmatic definition used to select patients with ‘some degree’ of HER2 protein expression adopting a test and a scoring system already implemented in the routine clinical practice,” said Dr. Bianchini, head of the breast cancer group and head of clinical translational and immunotherapy research at IRCCS Ospedale, San Raffaele, Milan.

However, the current definition may be inadequate, he said, explaining that the ongoing DESTINY-Breast06 study “will challenge the current definition of what we consider HER2-low definition,” potentially extending the T-DXd indication to HER2 ultra-low.

Furthermore, current HER2 testing was designed to discriminate cases with high abundant protein – not for the low HER2 dynamic range, which leads to technical inaccuracy.

Given these considerations, he suggested considering a new biopsy, if feasible, in patients with an immunohistochemistry (IHC) score of 0 in all tumor biopsies, and having a revision performed by the pathologist.

In patients with an IHC score of 1 or greater only in one biopsy, there is no need to confirm the HER2-low status, he said.

DESTINY-Breast04 is funded by Daiichi Sankyo Inc. and AstraZeneca. Dr. Modi reported relationships with Daiichi Sankyo, Genentech, AstraZeneca, Seagen, and MacroGenics. Dr. Bianchini reported relationships with AstraZeneca, Daiichi Sankyo, Gilead, MSD, Seagen, Roche, Sanofi, Lilly, EISAI, Novartis, Pfizer, Stemline, Exact Science, and Agendia.

A small trial headed by MD Anderson Cancer Center, Houston, has helped to further identify women who can safely skip surgery after neoadjuvant therapy for early breast cancer.

Among 50 women in the study with cT1-2N0-1M0 triple negative or HER2-positive disease, 31 (62%) had a complete pathologic response (pCR) to neoadjuvant therapy on image-guided vacuum-assisted core biopsy (VACB).

They went onto whole breast radiation with a boost, but given their response to neoadjuvant treatment and the accuracy of VACB, the women did not have surgery.

So far, it seems to have been the right call: At 3 years, there’s been no tumor recurrences and disease-free and overall survival are both 100%.

Eliminating “breast surgery in highly-selected patients with image-guided VACB-determined pCR following” neoadjuvant systemic therapy has “very promising 3-year results,” lead investigator Henry M. Kuerer, MD, PhD, a breast cancer surgeon at MD Anderson, who presented the findings at the European Society for Medical Oncology (ESMO) 2023 annual meeting.

The study speaks to a trend in breast cancer toward deescalation of treatment – particularly surgery – to save women from the side effects of treatments they don’t need.

With the success of modern systemic therapy, “it’s only natural that we think this way,” said Ava Kwong, PhD, chief of breast surgery at the University of Hong Kong, who discussed Dr. Kuerer’s presentation at the meeting.

“This study is really important,” she said. “It’s addressing a very important question whether we can omit surgery in certain groups of patients ... We do want to deescalate surgery,” and the study results are “very good,” she said.

However, larger trials with longer follow-up are needed to draw any firm conclusions, she said.

Dr. Kuerer agreed. He and his team will continue to follow the study subjects, and they have opened up a new trial with 100 patients. A similar study is ongoing in Korea, as well, he noted.
 

Study details

Women in the trial were a median of 60.4 years old; 58% had HER2-positive and the rest triple-negative unicentric breast cancer. Mean baseline tumor size was 2.8 cm. Just 12% of the participants had lymph node involvement. Neoadjuvant systemic therapy was clinician’s choice.

Breast lesions had to shrink to less than 2 cm on imaging after systemic therapy to be eligible for the study, and a minimum of 12 cores had to be obtained on VACB.

The 38% of women in the study with residual disease after systemic treatment went on to surgery.

Two patients were circulating tumor cell (CTC)-positive at baseline, two were positive at 6 months, and one at 12 months. No patients had CTCs detected at more than one timepoint.

The work was funded by the National Cancer Institute. Dr. Kuerer is an adviser for Merck. Dr. Kwong is an adviser/speaker/reviewer/author for Stryker, AstraZeneca, Merck, and Roche. She also disclosed research funding from Merck, Roche, and Gilead and funding for genetic testing from AstraZeneca.

A small trial headed by MD Anderson Cancer Center, Houston, has helped to further identify women who can safely skip surgery after neoadjuvant therapy for early breast cancer.

Among 50 women in the study with cT1-2N0-1M0 triple negative or HER2-positive disease, 31 (62%) had a complete pathologic response (pCR) to neoadjuvant therapy on image-guided vacuum-assisted core biopsy (VACB).

They went onto whole breast radiation with a boost, but given their response to neoadjuvant treatment and the accuracy of VACB, the women did not have surgery.

So far, it seems to have been the right call: At 3 years, there’s been no tumor recurrences and disease-free and overall survival are both 100%.

Eliminating “breast surgery in highly-selected patients with image-guided VACB-determined pCR following” neoadjuvant systemic therapy has “very promising 3-year results,” lead investigator Henry M. Kuerer, MD, PhD, a breast cancer surgeon at MD Anderson, who presented the findings at the European Society for Medical Oncology (ESMO) 2023 annual meeting.

The study speaks to a trend in breast cancer toward deescalation of treatment – particularly surgery – to save women from the side effects of treatments they don’t need.

With the success of modern systemic therapy, “it’s only natural that we think this way,” said Ava Kwong, PhD, chief of breast surgery at the University of Hong Kong, who discussed Dr. Kuerer’s presentation at the meeting.

“This study is really important,” she said. “It’s addressing a very important question whether we can omit surgery in certain groups of patients ... We do want to deescalate surgery,” and the study results are “very good,” she said.

However, larger trials with longer follow-up are needed to draw any firm conclusions, she said.

Dr. Kuerer agreed. He and his team will continue to follow the study subjects, and they have opened up a new trial with 100 patients. A similar study is ongoing in Korea, as well, he noted.
 

Study details

Women in the trial were a median of 60.4 years old; 58% had HER2-positive and the rest triple-negative unicentric breast cancer. Mean baseline tumor size was 2.8 cm. Just 12% of the participants had lymph node involvement. Neoadjuvant systemic therapy was clinician’s choice.

Breast lesions had to shrink to less than 2 cm on imaging after systemic therapy to be eligible for the study, and a minimum of 12 cores had to be obtained on VACB.

The 38% of women in the study with residual disease after systemic treatment went on to surgery.

Two patients were circulating tumor cell (CTC)-positive at baseline, two were positive at 6 months, and one at 12 months. No patients had CTCs detected at more than one timepoint.

The work was funded by the National Cancer Institute. Dr. Kuerer is an adviser for Merck. Dr. Kwong is an adviser/speaker/reviewer/author for Stryker, AstraZeneca, Merck, and Roche. She also disclosed research funding from Merck, Roche, and Gilead and funding for genetic testing from AstraZeneca.

A small trial headed by MD Anderson Cancer Center, Houston, has helped to further identify women who can safely skip surgery after neoadjuvant therapy for early breast cancer.

Among 50 women in the study with cT1-2N0-1M0 triple negative or HER2-positive disease, 31 (62%) had a complete pathologic response (pCR) to neoadjuvant therapy on image-guided vacuum-assisted core biopsy (VACB).

They went onto whole breast radiation with a boost, but given their response to neoadjuvant treatment and the accuracy of VACB, the women did not have surgery.

So far, it seems to have been the right call: At 3 years, there’s been no tumor recurrences and disease-free and overall survival are both 100%.

Eliminating “breast surgery in highly-selected patients with image-guided VACB-determined pCR following” neoadjuvant systemic therapy has “very promising 3-year results,” lead investigator Henry M. Kuerer, MD, PhD, a breast cancer surgeon at MD Anderson, who presented the findings at the European Society for Medical Oncology (ESMO) 2023 annual meeting.

The study speaks to a trend in breast cancer toward deescalation of treatment – particularly surgery – to save women from the side effects of treatments they don’t need.

With the success of modern systemic therapy, “it’s only natural that we think this way,” said Ava Kwong, PhD, chief of breast surgery at the University of Hong Kong, who discussed Dr. Kuerer’s presentation at the meeting.

“This study is really important,” she said. “It’s addressing a very important question whether we can omit surgery in certain groups of patients ... We do want to deescalate surgery,” and the study results are “very good,” she said.

However, larger trials with longer follow-up are needed to draw any firm conclusions, she said.

Dr. Kuerer agreed. He and his team will continue to follow the study subjects, and they have opened up a new trial with 100 patients. A similar study is ongoing in Korea, as well, he noted.
 

Study details

Women in the trial were a median of 60.4 years old; 58% had HER2-positive and the rest triple-negative unicentric breast cancer. Mean baseline tumor size was 2.8 cm. Just 12% of the participants had lymph node involvement. Neoadjuvant systemic therapy was clinician’s choice.

Breast lesions had to shrink to less than 2 cm on imaging after systemic therapy to be eligible for the study, and a minimum of 12 cores had to be obtained on VACB.

The 38% of women in the study with residual disease after systemic treatment went on to surgery.

Two patients were circulating tumor cell (CTC)-positive at baseline, two were positive at 6 months, and one at 12 months. No patients had CTCs detected at more than one timepoint.

The work was funded by the National Cancer Institute. Dr. Kuerer is an adviser for Merck. Dr. Kwong is an adviser/speaker/reviewer/author for Stryker, AstraZeneca, Merck, and Roche. She also disclosed research funding from Merck, Roche, and Gilead and funding for genetic testing from AstraZeneca.