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Cancer Identified Via Serum Metabolites, Lipids in Rheumatic Disease or Paraneoplasia
TOPLINE:
A diagnostic model based on the concentrations of four metabolites and one lipid ratio can reliably predict cancer in patients with rheumatic and musculoskeletal diseases (RMDs) or paraneoplasia, providing high sensitivity and specificity.
METHODOLOGY:
- The metabolome profile can differentiate between nonspecific inflammatory symptoms such as those associated with paraneoplastic conditions or RMDs, which can help accelerate cancer diagnosis and treatment.
- To assess if changes in the serum metabolome profile could indicate cancer in patients with RMD, researchers performed nuclear magnetic resonance analysis of the sera of patients with rheumatoid arthritis (RA) with a history of invasive cancer (n = 56; age, 69.9 years; 76.8% women) or without such history (n = 52; age, 56.1 years; 57.7% women).
- Blinded validation was conducted in a cohort of patients with RA or spondyloarthritis with or without a history of invasive cancer.
- Additionally, the model performance was tested in a cohort of patients having RA or spondyloarthritis with active cancer or cancer treatment, pulmonary and lymphoid type cancers, paraneoplastic syndromes, and facultative solid noninvasive precancerous lesions and nonmelanoma skin cancer; in samples prior to the development of malignancy; and in a cohort of patients with systemic lupus erythematosus (SLE).
- The final model comprised five variables. The goodness of fit of the model was described using the area under the receiver operating characteristic curve (AUC).
TAKEAWAY:
- Based on the concentrations of acetate, creatine, glycine, and formate and the L1/L6 lipid ratio, the diagnostic model yielded an excellent AUC (0.987) and high sensitivity (0.932) and specificity (0.946) for cancer diagnosis in patients with RA.
- The diagnostic model yielded an AUC of 0.937 in the blinded validation cohort of patients with RA and an AUC of 0.927 in the merged RA and spondyloarthritis cohort.
- Although the diagnostic model accurately diagnosed cancer in all the patients with paraneoplasia, it could do so accurately in only 50% of patients with noninvasive or in situ precancerous lesions and nonmelanoma skin cancers.
- The performance of the model was poor in the SLE cohort (AUC, 0.656), and it could not identify patients at risk for later invasive cancer development.
IN PRACTICE:
“This limited-invasive assay has considerable potential of high clinical value to facilitate timely diagnosis of cancer in paraneoplastic rheumatic syndromes as well as become a valuable active surveillance tool in RA and SpA [spondyloarthritis] patients with a high risk of developing cancer,” the authors wrote.
SOURCE:
The study, led by Karolina Gente, MHBA, Heidelberg University Hospital, Heidelberg, Germany, was published online on April 1, 2024, in Annals of the Rheumatic Diseases.
LIMITATIONS:
The limited invasiveness during sampling might account for the model’s inability to identify three early-stage, low-grade tumors and its nonreliability in identifying noninvasive facultative precancerous lesions and nonmelanoma skin cancers. Given its poor performance in the SLE cohort, the model may not be suitable for universal application in more systemic rheumatic diseases.
DISCLOSURES:
This study was supported by an unrestricted investigator-initiated grant from the Foundation Commission of the Medical Faculty, University of Heidelberg, Germany. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
A diagnostic model based on the concentrations of four metabolites and one lipid ratio can reliably predict cancer in patients with rheumatic and musculoskeletal diseases (RMDs) or paraneoplasia, providing high sensitivity and specificity.
METHODOLOGY:
- The metabolome profile can differentiate between nonspecific inflammatory symptoms such as those associated with paraneoplastic conditions or RMDs, which can help accelerate cancer diagnosis and treatment.
- To assess if changes in the serum metabolome profile could indicate cancer in patients with RMD, researchers performed nuclear magnetic resonance analysis of the sera of patients with rheumatoid arthritis (RA) with a history of invasive cancer (n = 56; age, 69.9 years; 76.8% women) or without such history (n = 52; age, 56.1 years; 57.7% women).
- Blinded validation was conducted in a cohort of patients with RA or spondyloarthritis with or without a history of invasive cancer.
- Additionally, the model performance was tested in a cohort of patients having RA or spondyloarthritis with active cancer or cancer treatment, pulmonary and lymphoid type cancers, paraneoplastic syndromes, and facultative solid noninvasive precancerous lesions and nonmelanoma skin cancer; in samples prior to the development of malignancy; and in a cohort of patients with systemic lupus erythematosus (SLE).
- The final model comprised five variables. The goodness of fit of the model was described using the area under the receiver operating characteristic curve (AUC).
TAKEAWAY:
- Based on the concentrations of acetate, creatine, glycine, and formate and the L1/L6 lipid ratio, the diagnostic model yielded an excellent AUC (0.987) and high sensitivity (0.932) and specificity (0.946) for cancer diagnosis in patients with RA.
- The diagnostic model yielded an AUC of 0.937 in the blinded validation cohort of patients with RA and an AUC of 0.927 in the merged RA and spondyloarthritis cohort.
- Although the diagnostic model accurately diagnosed cancer in all the patients with paraneoplasia, it could do so accurately in only 50% of patients with noninvasive or in situ precancerous lesions and nonmelanoma skin cancers.
- The performance of the model was poor in the SLE cohort (AUC, 0.656), and it could not identify patients at risk for later invasive cancer development.
IN PRACTICE:
“This limited-invasive assay has considerable potential of high clinical value to facilitate timely diagnosis of cancer in paraneoplastic rheumatic syndromes as well as become a valuable active surveillance tool in RA and SpA [spondyloarthritis] patients with a high risk of developing cancer,” the authors wrote.
SOURCE:
The study, led by Karolina Gente, MHBA, Heidelberg University Hospital, Heidelberg, Germany, was published online on April 1, 2024, in Annals of the Rheumatic Diseases.
LIMITATIONS:
The limited invasiveness during sampling might account for the model’s inability to identify three early-stage, low-grade tumors and its nonreliability in identifying noninvasive facultative precancerous lesions and nonmelanoma skin cancers. Given its poor performance in the SLE cohort, the model may not be suitable for universal application in more systemic rheumatic diseases.
DISCLOSURES:
This study was supported by an unrestricted investigator-initiated grant from the Foundation Commission of the Medical Faculty, University of Heidelberg, Germany. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
A diagnostic model based on the concentrations of four metabolites and one lipid ratio can reliably predict cancer in patients with rheumatic and musculoskeletal diseases (RMDs) or paraneoplasia, providing high sensitivity and specificity.
METHODOLOGY:
- The metabolome profile can differentiate between nonspecific inflammatory symptoms such as those associated with paraneoplastic conditions or RMDs, which can help accelerate cancer diagnosis and treatment.
- To assess if changes in the serum metabolome profile could indicate cancer in patients with RMD, researchers performed nuclear magnetic resonance analysis of the sera of patients with rheumatoid arthritis (RA) with a history of invasive cancer (n = 56; age, 69.9 years; 76.8% women) or without such history (n = 52; age, 56.1 years; 57.7% women).
- Blinded validation was conducted in a cohort of patients with RA or spondyloarthritis with or without a history of invasive cancer.
- Additionally, the model performance was tested in a cohort of patients having RA or spondyloarthritis with active cancer or cancer treatment, pulmonary and lymphoid type cancers, paraneoplastic syndromes, and facultative solid noninvasive precancerous lesions and nonmelanoma skin cancer; in samples prior to the development of malignancy; and in a cohort of patients with systemic lupus erythematosus (SLE).
- The final model comprised five variables. The goodness of fit of the model was described using the area under the receiver operating characteristic curve (AUC).
TAKEAWAY:
- Based on the concentrations of acetate, creatine, glycine, and formate and the L1/L6 lipid ratio, the diagnostic model yielded an excellent AUC (0.987) and high sensitivity (0.932) and specificity (0.946) for cancer diagnosis in patients with RA.
- The diagnostic model yielded an AUC of 0.937 in the blinded validation cohort of patients with RA and an AUC of 0.927 in the merged RA and spondyloarthritis cohort.
- Although the diagnostic model accurately diagnosed cancer in all the patients with paraneoplasia, it could do so accurately in only 50% of patients with noninvasive or in situ precancerous lesions and nonmelanoma skin cancers.
- The performance of the model was poor in the SLE cohort (AUC, 0.656), and it could not identify patients at risk for later invasive cancer development.
IN PRACTICE:
“This limited-invasive assay has considerable potential of high clinical value to facilitate timely diagnosis of cancer in paraneoplastic rheumatic syndromes as well as become a valuable active surveillance tool in RA and SpA [spondyloarthritis] patients with a high risk of developing cancer,” the authors wrote.
SOURCE:
The study, led by Karolina Gente, MHBA, Heidelberg University Hospital, Heidelberg, Germany, was published online on April 1, 2024, in Annals of the Rheumatic Diseases.
LIMITATIONS:
The limited invasiveness during sampling might account for the model’s inability to identify three early-stage, low-grade tumors and its nonreliability in identifying noninvasive facultative precancerous lesions and nonmelanoma skin cancers. Given its poor performance in the SLE cohort, the model may not be suitable for universal application in more systemic rheumatic diseases.
DISCLOSURES:
This study was supported by an unrestricted investigator-initiated grant from the Foundation Commission of the Medical Faculty, University of Heidelberg, Germany. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Molecular Classification of Endometrial Carcinomas
Historically, endometrial cancer has been classified as type I or type II. Type I endometrial cancers are typically estrogen driven, low grade, with endometrioid histology, and have a more favorable prognosis. In contrast, type II endometrial cancers are typically high grade, have more aggressive histologies (eg, serous or clear cell), and have a poorer prognosis.1
While this system provides a helpful schema for understanding endometrial cancers, it fails to represent the immense variation of biologic behavior and outcomes in endometrial cancers and oversimplifies what has come to be understood as a complex and molecularly diverse disease.
In 2013, The Cancer Genome Atlas (TCGA) performed genomic, transcriptomic, and proteomic characterization of 373 endometrial carcinomas. They identified four categories with distinct genetic profiles corresponding to clinical outcomes: 1) DNA polymerase epsilon (POLE) mutated; 2) mismatch repair deficient; 3) copy number high/p53 abnormal; and 4) copy number low/no specific molecular profile.2 By providing both predictive and prognostic information, these molecular features may be incorporated into treatment planning decisions in the future.
The POLE-mutated subtype are endometrial cancers with recurrent mutations in the POLE gene, which is involved in DNA replication and repair. POLE mutations occur in about 5%-10% of endometrial cancers. Despite some more aggressive histopathologic findings (eg, higher grade, deeper myometrial invasion, positive lymphovascular space invasion), recurrences rarely occur, and patients with POLE mutations have the best prognosis of the four molecular subtypes, with a 5-year recurrence-free survival of 92%-100%.3
The mismatch repair–deficient (MMRd) subtype are endometrial cancers with abnormalities in any of the mismatch repair proteins (MLH1, PMS2, MSH2, MSH6). These alterations may result from hereditary or somatic mutations in any of the MMR genes or epigenetic changes in the MLH1 promoter. Germ-line mutations are associated with Lynch syndrome; thus, patients found to have a germ-line mutation in any of the MMR genes necessitate a genetics referral. The MMRd subtype accounts for about 20%-30% of endometrial cancers, and patients with MMRd tumors have an intermediate prognosis, with a 5-year recurrence-free survival of about 70%.3. These tumors are more responsive to the use of immunotherapy checkpoint inhibitors. Two recent landmark trials showed improved outcomes in patients with advanced MMRd endometrial cancer treated with immune checkpoint inhibitors in addition to standard chemotherapy.4,5
The worst prognosis belongs to the copy number high subgroup, which accounts for approximately 10% of endometrial cancers. Five-year recurrence-free survival is ~50%.3 These tumors often contain TP53 mutations and are composed of aggressive histologies, such as serous, clear cell, high-grade endometrioid, and carcinosarcomas. Recent data suggests that human epidermal growth factor receptor 2 (HER2) amplification may also be prevalent in this subgroup.6
Endometrial cancers that lack any of the above alterations fall into the no specific molecular profile (NSMP) or copy number low subgroup. Mutations in other genes, such as PTEN, PIK3CA, CTNNB1, KRAS, and ARID1A, are often present in these tumors. As the most common subtype, this heterogeneous group accounts for about 50% of all endometrial cancers. These tumors frequently comprise endometrioid histology with estrogen and progesterone receptor positivity, high rates of response to hormonal therapy, and an overall intermediate to favorable prognosis, with a 5-year recurrence-free survival of ~75%.3
The use of whole-genome sequencing in TCGA limits the clinical applicability of testing because of the cost and complex methodologies involved. Multiple algorithms have been developed in the interim that approximate TCGA subtypes using relatively less expensive and more widely available testing methods, such as immunohistochemistry and next-generation sequencing. In the ProMisE algorithm, immunohistochemistry for p53 and MMR proteins is used as a surrogate for copy number high and MMRd tumors, respectively, and targeted sequencing is used to identify POLE mutations.7
Full molecular classification of endometrial tumors provides important prognostic information and allows for incorporation into treatment planning. To this end, the new 2023 International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging incorporates an option for the addition of molecular subtype, with the stance that it allows for better prognostic prediction.8 While complete molecular classification is not required, it is encouraged. Furthermore, several clinical trials are currently investigating different treatment regimens based on these distinct molecular profiles.
Dr. Haag is a gynecologic oncology fellow in the Department of Obstetrics and Gynecology, University of North Carolina Hospitals, Chapel Hill. Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill. They have no conflicts of interest.
References
1. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecologic Oncology. 1983;15(1):10-17.
2. Kandoth C et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67-73.
3. León-Castillo A et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: Impact on prognosis and benefit from adjuvant therapy. J Clin Oncology. 2020;38(29):3388-3397.
4. Mirza MR et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388(23):2145-2158.
5. Eskander RN et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med. 2023;388(23):2159-2170.
6. Talia KL et al. The role of HER2 as a therapeutic biomarker in gynaecological malignancy: Potential for use beyond uterine serous carcinoma. Pathology. 2023;55(1):8-18.
7. Kommoss S et al. Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. Annals Oncology. 2018;29(5):1180-1188.
8. Berek JS et al. FIGO staging of endometrial cancer: 2023. Int J Gynaecol Obstet. 2023;162(2):383-394.
Historically, endometrial cancer has been classified as type I or type II. Type I endometrial cancers are typically estrogen driven, low grade, with endometrioid histology, and have a more favorable prognosis. In contrast, type II endometrial cancers are typically high grade, have more aggressive histologies (eg, serous or clear cell), and have a poorer prognosis.1
While this system provides a helpful schema for understanding endometrial cancers, it fails to represent the immense variation of biologic behavior and outcomes in endometrial cancers and oversimplifies what has come to be understood as a complex and molecularly diverse disease.
In 2013, The Cancer Genome Atlas (TCGA) performed genomic, transcriptomic, and proteomic characterization of 373 endometrial carcinomas. They identified four categories with distinct genetic profiles corresponding to clinical outcomes: 1) DNA polymerase epsilon (POLE) mutated; 2) mismatch repair deficient; 3) copy number high/p53 abnormal; and 4) copy number low/no specific molecular profile.2 By providing both predictive and prognostic information, these molecular features may be incorporated into treatment planning decisions in the future.
The POLE-mutated subtype are endometrial cancers with recurrent mutations in the POLE gene, which is involved in DNA replication and repair. POLE mutations occur in about 5%-10% of endometrial cancers. Despite some more aggressive histopathologic findings (eg, higher grade, deeper myometrial invasion, positive lymphovascular space invasion), recurrences rarely occur, and patients with POLE mutations have the best prognosis of the four molecular subtypes, with a 5-year recurrence-free survival of 92%-100%.3
The mismatch repair–deficient (MMRd) subtype are endometrial cancers with abnormalities in any of the mismatch repair proteins (MLH1, PMS2, MSH2, MSH6). These alterations may result from hereditary or somatic mutations in any of the MMR genes or epigenetic changes in the MLH1 promoter. Germ-line mutations are associated with Lynch syndrome; thus, patients found to have a germ-line mutation in any of the MMR genes necessitate a genetics referral. The MMRd subtype accounts for about 20%-30% of endometrial cancers, and patients with MMRd tumors have an intermediate prognosis, with a 5-year recurrence-free survival of about 70%.3. These tumors are more responsive to the use of immunotherapy checkpoint inhibitors. Two recent landmark trials showed improved outcomes in patients with advanced MMRd endometrial cancer treated with immune checkpoint inhibitors in addition to standard chemotherapy.4,5
The worst prognosis belongs to the copy number high subgroup, which accounts for approximately 10% of endometrial cancers. Five-year recurrence-free survival is ~50%.3 These tumors often contain TP53 mutations and are composed of aggressive histologies, such as serous, clear cell, high-grade endometrioid, and carcinosarcomas. Recent data suggests that human epidermal growth factor receptor 2 (HER2) amplification may also be prevalent in this subgroup.6
Endometrial cancers that lack any of the above alterations fall into the no specific molecular profile (NSMP) or copy number low subgroup. Mutations in other genes, such as PTEN, PIK3CA, CTNNB1, KRAS, and ARID1A, are often present in these tumors. As the most common subtype, this heterogeneous group accounts for about 50% of all endometrial cancers. These tumors frequently comprise endometrioid histology with estrogen and progesterone receptor positivity, high rates of response to hormonal therapy, and an overall intermediate to favorable prognosis, with a 5-year recurrence-free survival of ~75%.3
The use of whole-genome sequencing in TCGA limits the clinical applicability of testing because of the cost and complex methodologies involved. Multiple algorithms have been developed in the interim that approximate TCGA subtypes using relatively less expensive and more widely available testing methods, such as immunohistochemistry and next-generation sequencing. In the ProMisE algorithm, immunohistochemistry for p53 and MMR proteins is used as a surrogate for copy number high and MMRd tumors, respectively, and targeted sequencing is used to identify POLE mutations.7
Full molecular classification of endometrial tumors provides important prognostic information and allows for incorporation into treatment planning. To this end, the new 2023 International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging incorporates an option for the addition of molecular subtype, with the stance that it allows for better prognostic prediction.8 While complete molecular classification is not required, it is encouraged. Furthermore, several clinical trials are currently investigating different treatment regimens based on these distinct molecular profiles.
Dr. Haag is a gynecologic oncology fellow in the Department of Obstetrics and Gynecology, University of North Carolina Hospitals, Chapel Hill. Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill. They have no conflicts of interest.
References
1. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecologic Oncology. 1983;15(1):10-17.
2. Kandoth C et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67-73.
3. León-Castillo A et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: Impact on prognosis and benefit from adjuvant therapy. J Clin Oncology. 2020;38(29):3388-3397.
4. Mirza MR et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388(23):2145-2158.
5. Eskander RN et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med. 2023;388(23):2159-2170.
6. Talia KL et al. The role of HER2 as a therapeutic biomarker in gynaecological malignancy: Potential for use beyond uterine serous carcinoma. Pathology. 2023;55(1):8-18.
7. Kommoss S et al. Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. Annals Oncology. 2018;29(5):1180-1188.
8. Berek JS et al. FIGO staging of endometrial cancer: 2023. Int J Gynaecol Obstet. 2023;162(2):383-394.
Historically, endometrial cancer has been classified as type I or type II. Type I endometrial cancers are typically estrogen driven, low grade, with endometrioid histology, and have a more favorable prognosis. In contrast, type II endometrial cancers are typically high grade, have more aggressive histologies (eg, serous or clear cell), and have a poorer prognosis.1
While this system provides a helpful schema for understanding endometrial cancers, it fails to represent the immense variation of biologic behavior and outcomes in endometrial cancers and oversimplifies what has come to be understood as a complex and molecularly diverse disease.
In 2013, The Cancer Genome Atlas (TCGA) performed genomic, transcriptomic, and proteomic characterization of 373 endometrial carcinomas. They identified four categories with distinct genetic profiles corresponding to clinical outcomes: 1) DNA polymerase epsilon (POLE) mutated; 2) mismatch repair deficient; 3) copy number high/p53 abnormal; and 4) copy number low/no specific molecular profile.2 By providing both predictive and prognostic information, these molecular features may be incorporated into treatment planning decisions in the future.
The POLE-mutated subtype are endometrial cancers with recurrent mutations in the POLE gene, which is involved in DNA replication and repair. POLE mutations occur in about 5%-10% of endometrial cancers. Despite some more aggressive histopathologic findings (eg, higher grade, deeper myometrial invasion, positive lymphovascular space invasion), recurrences rarely occur, and patients with POLE mutations have the best prognosis of the four molecular subtypes, with a 5-year recurrence-free survival of 92%-100%.3
The mismatch repair–deficient (MMRd) subtype are endometrial cancers with abnormalities in any of the mismatch repair proteins (MLH1, PMS2, MSH2, MSH6). These alterations may result from hereditary or somatic mutations in any of the MMR genes or epigenetic changes in the MLH1 promoter. Germ-line mutations are associated with Lynch syndrome; thus, patients found to have a germ-line mutation in any of the MMR genes necessitate a genetics referral. The MMRd subtype accounts for about 20%-30% of endometrial cancers, and patients with MMRd tumors have an intermediate prognosis, with a 5-year recurrence-free survival of about 70%.3. These tumors are more responsive to the use of immunotherapy checkpoint inhibitors. Two recent landmark trials showed improved outcomes in patients with advanced MMRd endometrial cancer treated with immune checkpoint inhibitors in addition to standard chemotherapy.4,5
The worst prognosis belongs to the copy number high subgroup, which accounts for approximately 10% of endometrial cancers. Five-year recurrence-free survival is ~50%.3 These tumors often contain TP53 mutations and are composed of aggressive histologies, such as serous, clear cell, high-grade endometrioid, and carcinosarcomas. Recent data suggests that human epidermal growth factor receptor 2 (HER2) amplification may also be prevalent in this subgroup.6
Endometrial cancers that lack any of the above alterations fall into the no specific molecular profile (NSMP) or copy number low subgroup. Mutations in other genes, such as PTEN, PIK3CA, CTNNB1, KRAS, and ARID1A, are often present in these tumors. As the most common subtype, this heterogeneous group accounts for about 50% of all endometrial cancers. These tumors frequently comprise endometrioid histology with estrogen and progesterone receptor positivity, high rates of response to hormonal therapy, and an overall intermediate to favorable prognosis, with a 5-year recurrence-free survival of ~75%.3
The use of whole-genome sequencing in TCGA limits the clinical applicability of testing because of the cost and complex methodologies involved. Multiple algorithms have been developed in the interim that approximate TCGA subtypes using relatively less expensive and more widely available testing methods, such as immunohistochemistry and next-generation sequencing. In the ProMisE algorithm, immunohistochemistry for p53 and MMR proteins is used as a surrogate for copy number high and MMRd tumors, respectively, and targeted sequencing is used to identify POLE mutations.7
Full molecular classification of endometrial tumors provides important prognostic information and allows for incorporation into treatment planning. To this end, the new 2023 International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging incorporates an option for the addition of molecular subtype, with the stance that it allows for better prognostic prediction.8 While complete molecular classification is not required, it is encouraged. Furthermore, several clinical trials are currently investigating different treatment regimens based on these distinct molecular profiles.
Dr. Haag is a gynecologic oncology fellow in the Department of Obstetrics and Gynecology, University of North Carolina Hospitals, Chapel Hill. Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill. They have no conflicts of interest.
References
1. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecologic Oncology. 1983;15(1):10-17.
2. Kandoth C et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67-73.
3. León-Castillo A et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: Impact on prognosis and benefit from adjuvant therapy. J Clin Oncology. 2020;38(29):3388-3397.
4. Mirza MR et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388(23):2145-2158.
5. Eskander RN et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med. 2023;388(23):2159-2170.
6. Talia KL et al. The role of HER2 as a therapeutic biomarker in gynaecological malignancy: Potential for use beyond uterine serous carcinoma. Pathology. 2023;55(1):8-18.
7. Kommoss S et al. Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. Annals Oncology. 2018;29(5):1180-1188.
8. Berek JS et al. FIGO staging of endometrial cancer: 2023. Int J Gynaecol Obstet. 2023;162(2):383-394.
Statin Use Improves Cancer-Specific Survival in Older Women With Breast Cancer
Key clinical point: Use of a statin after breast cancer (BC) diagnosis improved survival in older women (age ≥ 66 years) with localized and regional stage disease, particularly in those with the hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) subtype.
Major finding: Use vs no use of a statin postdiagnosis was associated with a 15% reduced risk for BC-specific mortality (hazard ratio 0.85; 95% CI 0.75-0.96), with the effect being more pronounced women with HR+/HER2− BC (hazard ratio 0.71; 95% CI 0.57-0.88). There was no significant association between postdiagnosis statin use and the risk for BC recurrence (hazard ratio 1.05; 95% CI 0.91-1.21).
Study details: This retrospective cohort study included women with localized and regional stage BC from the Surveillance, Epidemiology, and End Results (SEER)–Medicare database who were assessed for mortality (n = 38,858) and recurrence (n = 28,522), of whom 8836 and 6475 used a statin postdiagnosis, respectively.
Disclosures: This study was supported by the US National Cancer Institute, National Institutes of Health. The authors declared no conflicts of interest.
Source: Guo H, Malone KE, Heckbert SR, Li CI. Statin use and risks of breast cancer recurrence and mortality. Cancer. 2024 (May 6). doi: 10.1002/cncr.35362 Source
Key clinical point: Use of a statin after breast cancer (BC) diagnosis improved survival in older women (age ≥ 66 years) with localized and regional stage disease, particularly in those with the hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) subtype.
Major finding: Use vs no use of a statin postdiagnosis was associated with a 15% reduced risk for BC-specific mortality (hazard ratio 0.85; 95% CI 0.75-0.96), with the effect being more pronounced women with HR+/HER2− BC (hazard ratio 0.71; 95% CI 0.57-0.88). There was no significant association between postdiagnosis statin use and the risk for BC recurrence (hazard ratio 1.05; 95% CI 0.91-1.21).
Study details: This retrospective cohort study included women with localized and regional stage BC from the Surveillance, Epidemiology, and End Results (SEER)–Medicare database who were assessed for mortality (n = 38,858) and recurrence (n = 28,522), of whom 8836 and 6475 used a statin postdiagnosis, respectively.
Disclosures: This study was supported by the US National Cancer Institute, National Institutes of Health. The authors declared no conflicts of interest.
Source: Guo H, Malone KE, Heckbert SR, Li CI. Statin use and risks of breast cancer recurrence and mortality. Cancer. 2024 (May 6). doi: 10.1002/cncr.35362 Source
Key clinical point: Use of a statin after breast cancer (BC) diagnosis improved survival in older women (age ≥ 66 years) with localized and regional stage disease, particularly in those with the hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2−) subtype.
Major finding: Use vs no use of a statin postdiagnosis was associated with a 15% reduced risk for BC-specific mortality (hazard ratio 0.85; 95% CI 0.75-0.96), with the effect being more pronounced women with HR+/HER2− BC (hazard ratio 0.71; 95% CI 0.57-0.88). There was no significant association between postdiagnosis statin use and the risk for BC recurrence (hazard ratio 1.05; 95% CI 0.91-1.21).
Study details: This retrospective cohort study included women with localized and regional stage BC from the Surveillance, Epidemiology, and End Results (SEER)–Medicare database who were assessed for mortality (n = 38,858) and recurrence (n = 28,522), of whom 8836 and 6475 used a statin postdiagnosis, respectively.
Disclosures: This study was supported by the US National Cancer Institute, National Institutes of Health. The authors declared no conflicts of interest.
Source: Guo H, Malone KE, Heckbert SR, Li CI. Statin use and risks of breast cancer recurrence and mortality. Cancer. 2024 (May 6). doi: 10.1002/cncr.35362 Source
SLNB Not Required Before Neoadjuvant Chemotherapy in Node-Negative Breast Cancer
Key clinical point: Sentinel lymph node biopsy (SLNB) performed before vs after neoadjuvant chemotherapy (NACT) showed a higher axillary lymph node dissection rate and no overall survival (OS) benefits in patients with clinically lymph node-negative (cN0) breast cancer (BC).
Major finding: The axillary lymph node dissection rate was significantly higher for SLNB performed before vs after NACT (29.9% vs 7.4%; P < .001; odds ratio 5.35; P = .002). Moreover, the 4-year overall survival rate was significantly compromised when SLNB was performed before vs after NACT (88.4% vs 95.7%; hazard ratio 0.21; P = .009).
Study details: This retrospective observational study included 310 patients with cN0 BC, of whom 107 and 203 patients underwent SLNB before and after NACT, respectively.
Disclosures: This study did not receive any specific funding except Open Access funding from Springer Nature. The authors declared no financial conflicts of interest. Two authors declared non-financial ties with various sources.
Source: Fernandez-Gonzalez S, Falo C, Pla MJ, et al. Sentinel lymph node biopsy before and after neoadjuvant chemotherapy in cN0 breast cancer patients: Impact on axillary morbidity and survival—A propensity score cohort study. Breast Cancer Res Treat. 2024 (Apr 18). doi: 10.1007/s10549-024-07274-1 Source
Key clinical point: Sentinel lymph node biopsy (SLNB) performed before vs after neoadjuvant chemotherapy (NACT) showed a higher axillary lymph node dissection rate and no overall survival (OS) benefits in patients with clinically lymph node-negative (cN0) breast cancer (BC).
Major finding: The axillary lymph node dissection rate was significantly higher for SLNB performed before vs after NACT (29.9% vs 7.4%; P < .001; odds ratio 5.35; P = .002). Moreover, the 4-year overall survival rate was significantly compromised when SLNB was performed before vs after NACT (88.4% vs 95.7%; hazard ratio 0.21; P = .009).
Study details: This retrospective observational study included 310 patients with cN0 BC, of whom 107 and 203 patients underwent SLNB before and after NACT, respectively.
Disclosures: This study did not receive any specific funding except Open Access funding from Springer Nature. The authors declared no financial conflicts of interest. Two authors declared non-financial ties with various sources.
Source: Fernandez-Gonzalez S, Falo C, Pla MJ, et al. Sentinel lymph node biopsy before and after neoadjuvant chemotherapy in cN0 breast cancer patients: Impact on axillary morbidity and survival—A propensity score cohort study. Breast Cancer Res Treat. 2024 (Apr 18). doi: 10.1007/s10549-024-07274-1 Source
Key clinical point: Sentinel lymph node biopsy (SLNB) performed before vs after neoadjuvant chemotherapy (NACT) showed a higher axillary lymph node dissection rate and no overall survival (OS) benefits in patients with clinically lymph node-negative (cN0) breast cancer (BC).
Major finding: The axillary lymph node dissection rate was significantly higher for SLNB performed before vs after NACT (29.9% vs 7.4%; P < .001; odds ratio 5.35; P = .002). Moreover, the 4-year overall survival rate was significantly compromised when SLNB was performed before vs after NACT (88.4% vs 95.7%; hazard ratio 0.21; P = .009).
Study details: This retrospective observational study included 310 patients with cN0 BC, of whom 107 and 203 patients underwent SLNB before and after NACT, respectively.
Disclosures: This study did not receive any specific funding except Open Access funding from Springer Nature. The authors declared no financial conflicts of interest. Two authors declared non-financial ties with various sources.
Source: Fernandez-Gonzalez S, Falo C, Pla MJ, et al. Sentinel lymph node biopsy before and after neoadjuvant chemotherapy in cN0 breast cancer patients: Impact on axillary morbidity and survival—A propensity score cohort study. Breast Cancer Res Treat. 2024 (Apr 18). doi: 10.1007/s10549-024-07274-1 Source
Trastuzumab Deruxtecan Bests Trastuzumab Emtansine in HER2+ BC With or Without Brain Metastases
Key clinical point: Trastuzumab deruxtecan demonstrated superior efficacy over trastuzumab emtansine as second-line treatment in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) with or without brain metastases.
Major finding: Trastuzumab deruxtecan led to significantly longer median progression-free survival (15.0 vs 3.0 months; hazard ratio 0.25; 95% CI 0.13-0.45) and higher systemic (67.4% vs 20.5%) and intracranial (65.7% vs 34.3%) objective response rates than trastuzumab emtansine in patients with brain metastases. Outcomes were similar in patients without brain metastases.
Study details: This exploratory analysis of the phase 3 DESTINY-Breast03 trial included 524 patients with HER2+ metastatic BC with or without brain metastases who were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine after their disease progressed with trastuzumab and taxane treatment.
Disclosures: This study was supported by Daiichi Sankyo and AstraZeneca. Six authors declared being current or former employees or holding stock or stock options of Daiichi Sankyo or AstraZeneca. Several authors declared having ties to various sources, including Daiichi Sankyo and AstraZeneca.
Source: Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial. ESMO Open. 2024;109294 (Apr 24). doi: 10.1016/j.esmoop.2024.102924 Source
Key clinical point: Trastuzumab deruxtecan demonstrated superior efficacy over trastuzumab emtansine as second-line treatment in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) with or without brain metastases.
Major finding: Trastuzumab deruxtecan led to significantly longer median progression-free survival (15.0 vs 3.0 months; hazard ratio 0.25; 95% CI 0.13-0.45) and higher systemic (67.4% vs 20.5%) and intracranial (65.7% vs 34.3%) objective response rates than trastuzumab emtansine in patients with brain metastases. Outcomes were similar in patients without brain metastases.
Study details: This exploratory analysis of the phase 3 DESTINY-Breast03 trial included 524 patients with HER2+ metastatic BC with or without brain metastases who were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine after their disease progressed with trastuzumab and taxane treatment.
Disclosures: This study was supported by Daiichi Sankyo and AstraZeneca. Six authors declared being current or former employees or holding stock or stock options of Daiichi Sankyo or AstraZeneca. Several authors declared having ties to various sources, including Daiichi Sankyo and AstraZeneca.
Source: Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial. ESMO Open. 2024;109294 (Apr 24). doi: 10.1016/j.esmoop.2024.102924 Source
Key clinical point: Trastuzumab deruxtecan demonstrated superior efficacy over trastuzumab emtansine as second-line treatment in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) with or without brain metastases.
Major finding: Trastuzumab deruxtecan led to significantly longer median progression-free survival (15.0 vs 3.0 months; hazard ratio 0.25; 95% CI 0.13-0.45) and higher systemic (67.4% vs 20.5%) and intracranial (65.7% vs 34.3%) objective response rates than trastuzumab emtansine in patients with brain metastases. Outcomes were similar in patients without brain metastases.
Study details: This exploratory analysis of the phase 3 DESTINY-Breast03 trial included 524 patients with HER2+ metastatic BC with or without brain metastases who were randomly assigned to receive trastuzumab deruxtecan or trastuzumab emtansine after their disease progressed with trastuzumab and taxane treatment.
Disclosures: This study was supported by Daiichi Sankyo and AstraZeneca. Six authors declared being current or former employees or holding stock or stock options of Daiichi Sankyo or AstraZeneca. Several authors declared having ties to various sources, including Daiichi Sankyo and AstraZeneca.
Source: Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial. ESMO Open. 2024;109294 (Apr 24). doi: 10.1016/j.esmoop.2024.102924 Source
Axillary Lymph Node Dissection Can Be Omitted After Nodal Downstaging With Chemotherapy in BC
Key clinical point: Axillary lymph node dissection (ALND) can be omitted in node-positive breast cancer (BC) as only 1% of patients who achieved nodal pathological complete response (pCR) with neoadjuvant chemotherapy reported axillary recurrence (AR) in 5 years.
Major finding: The AR rate was very low at 0.65% (95% CI 0.29%-1.30%) and 1.0% (95% CI 0.49%-2.00%) at 3 years and 5 years, respectively, in patients who omitted ALND and underwent targeted axillary dissection (TAD) or sentinel lymph node biopsy (SLNB). AR rates were comparable in both surgical cohorts at 3 years (P = .55).
Study details: This retrospective cohort study included 1144 patients with node-positive BC who achieved nodal pCR with neoadjuvant chemotherapy, of whom 58.2% and 41.8% underwent SLNB and TAD, respectively.
Disclosures: This study was supported in part by a US National Institutes of Health and US National Cancer Institute Cancer Center support grant. Several authors declared receiving personal fees, grants, or consulting fees from or having other ties with various sources.
Source: Montagna G, Mrdutt MM, Sun SX, et al. Omission of axillary dissection following nodal downstaging with neoadjuvant chemotherapy. JAMA Oncol. 2024 (Apr 25). doi: 10.1001/jamaoncol.2024.0578 Source
Key clinical point: Axillary lymph node dissection (ALND) can be omitted in node-positive breast cancer (BC) as only 1% of patients who achieved nodal pathological complete response (pCR) with neoadjuvant chemotherapy reported axillary recurrence (AR) in 5 years.
Major finding: The AR rate was very low at 0.65% (95% CI 0.29%-1.30%) and 1.0% (95% CI 0.49%-2.00%) at 3 years and 5 years, respectively, in patients who omitted ALND and underwent targeted axillary dissection (TAD) or sentinel lymph node biopsy (SLNB). AR rates were comparable in both surgical cohorts at 3 years (P = .55).
Study details: This retrospective cohort study included 1144 patients with node-positive BC who achieved nodal pCR with neoadjuvant chemotherapy, of whom 58.2% and 41.8% underwent SLNB and TAD, respectively.
Disclosures: This study was supported in part by a US National Institutes of Health and US National Cancer Institute Cancer Center support grant. Several authors declared receiving personal fees, grants, or consulting fees from or having other ties with various sources.
Source: Montagna G, Mrdutt MM, Sun SX, et al. Omission of axillary dissection following nodal downstaging with neoadjuvant chemotherapy. JAMA Oncol. 2024 (Apr 25). doi: 10.1001/jamaoncol.2024.0578 Source
Key clinical point: Axillary lymph node dissection (ALND) can be omitted in node-positive breast cancer (BC) as only 1% of patients who achieved nodal pathological complete response (pCR) with neoadjuvant chemotherapy reported axillary recurrence (AR) in 5 years.
Major finding: The AR rate was very low at 0.65% (95% CI 0.29%-1.30%) and 1.0% (95% CI 0.49%-2.00%) at 3 years and 5 years, respectively, in patients who omitted ALND and underwent targeted axillary dissection (TAD) or sentinel lymph node biopsy (SLNB). AR rates were comparable in both surgical cohorts at 3 years (P = .55).
Study details: This retrospective cohort study included 1144 patients with node-positive BC who achieved nodal pCR with neoadjuvant chemotherapy, of whom 58.2% and 41.8% underwent SLNB and TAD, respectively.
Disclosures: This study was supported in part by a US National Institutes of Health and US National Cancer Institute Cancer Center support grant. Several authors declared receiving personal fees, grants, or consulting fees from or having other ties with various sources.
Source: Montagna G, Mrdutt MM, Sun SX, et al. Omission of axillary dissection following nodal downstaging with neoadjuvant chemotherapy. JAMA Oncol. 2024 (Apr 25). doi: 10.1001/jamaoncol.2024.0578 Source
Postpartum BC Diagnosis Raises Mortality Risk in Women With BRCA Mutations
Key clinical point: Breast cancer (BC) diagnosed between five to <10 years postpartum (PP) was associated with a high mortality risk in women with young-onset BC (age ≤ 45 years) who had germline BRCA1/2 pathogenic variants (PV), particularly the BRCA1 mutation.
Major finding: Women with PPBC diagnosed within 5-10 years had an almost 1.5-fold higher mortality risk than nulliparous women (adjusted hazard ratio [aHR] 1.56; P = .03), with the risk being even more prominent in BRCA1 carriers (aHR 2.03; P = .02) and those with estrogen receptor-negative BC (aHR 3.12; P = .02).
Study details: This prospective cohort study included 903 women with germline BRCA1/2 PV diagnosed with stages I-III BC at age ≤ 45 years, of whom 224 were nulliparous at the time of BC diagnosis.
Disclosures: This study was supported by Oregon Health & Science University's Knight Cancer Institute, US National Institutes of Health, US National Cancer Institute, and other sources. Two authors declared receiving personal fees from various sources.
Source: Zhang Z, Ye S, Bernhardt SM, et al. Postpartum breast cancer and survival in women with germline BRCA pathogenic variants. JAMA Netw Open. 2024;7(4):e247421. doi: 10.1001/jamanetworkopen.2024.7421 Source
Key clinical point: Breast cancer (BC) diagnosed between five to <10 years postpartum (PP) was associated with a high mortality risk in women with young-onset BC (age ≤ 45 years) who had germline BRCA1/2 pathogenic variants (PV), particularly the BRCA1 mutation.
Major finding: Women with PPBC diagnosed within 5-10 years had an almost 1.5-fold higher mortality risk than nulliparous women (adjusted hazard ratio [aHR] 1.56; P = .03), with the risk being even more prominent in BRCA1 carriers (aHR 2.03; P = .02) and those with estrogen receptor-negative BC (aHR 3.12; P = .02).
Study details: This prospective cohort study included 903 women with germline BRCA1/2 PV diagnosed with stages I-III BC at age ≤ 45 years, of whom 224 were nulliparous at the time of BC diagnosis.
Disclosures: This study was supported by Oregon Health & Science University's Knight Cancer Institute, US National Institutes of Health, US National Cancer Institute, and other sources. Two authors declared receiving personal fees from various sources.
Source: Zhang Z, Ye S, Bernhardt SM, et al. Postpartum breast cancer and survival in women with germline BRCA pathogenic variants. JAMA Netw Open. 2024;7(4):e247421. doi: 10.1001/jamanetworkopen.2024.7421 Source
Key clinical point: Breast cancer (BC) diagnosed between five to <10 years postpartum (PP) was associated with a high mortality risk in women with young-onset BC (age ≤ 45 years) who had germline BRCA1/2 pathogenic variants (PV), particularly the BRCA1 mutation.
Major finding: Women with PPBC diagnosed within 5-10 years had an almost 1.5-fold higher mortality risk than nulliparous women (adjusted hazard ratio [aHR] 1.56; P = .03), with the risk being even more prominent in BRCA1 carriers (aHR 2.03; P = .02) and those with estrogen receptor-negative BC (aHR 3.12; P = .02).
Study details: This prospective cohort study included 903 women with germline BRCA1/2 PV diagnosed with stages I-III BC at age ≤ 45 years, of whom 224 were nulliparous at the time of BC diagnosis.
Disclosures: This study was supported by Oregon Health & Science University's Knight Cancer Institute, US National Institutes of Health, US National Cancer Institute, and other sources. Two authors declared receiving personal fees from various sources.
Source: Zhang Z, Ye S, Bernhardt SM, et al. Postpartum breast cancer and survival in women with germline BRCA pathogenic variants. JAMA Netw Open. 2024;7(4):e247421. doi: 10.1001/jamanetworkopen.2024.7421 Source
bDMARDs Preserve Renal Function in Most Patients With AA Amyloidosis
TOPLINE:
Treatment with biologic disease-modifying antirheumatic drugs (bDMARDs), particularly tocilizumab, can suppress inflammation and preserve renal function in a majority of patients with chronic inflammatory disorders who develop serum amyloid alpha (SAA) amyloidosis.
METHODOLOGY:
- AA amyloidosis, characterized by the misfolding of the SAA protein, is observed in patients with inflammatory diseases and can lead to progressive organ damage, including chronic kidney disease, malabsorption with cachexia, and cardiac failure.
- This monocentric, retrospective analysis assessed the effect of bDMARD therapy on inflammatory biomarker levels and renal outcomes in 83 patients with AA amyloidosis who were followed for a mean period of 4.82 years.
- The patients were stratified into three major subgroups depending on the cause of AA amyloidosis:
- Chronic inflammatory diseases (cid + AA; n = 34) such as rheumatoid arthritis, Crohn’s disease, and chronic infections
- Autoinflammatory syndromes (auto + AA; n = 24) such as familial Mediterranean fever (FMF) and cryopyrin-associated periodic syndrome (CAPS)
- Idiopathic AA (idio + AA; n = 25), wherein the primary disease could not be identified
- Tocilizumab was the most commonly used bDMARD in patients with cid + AA and idio + AA amyloidosis, and interleukin-1 inhibitors were prescribed to patients with auto + AA amyloidosis because tocilizumab has not been approved yet for FMF or CAPS treatment.
- All patients with AA amyloidosis had renal involvement, as confirmed by kidney biopsy.
TAKEAWAY:
- After bDMARD therapy, C-reactive protein levels reduced significantly from baseline to the last-documented visit in all subgroups, while SAA levels declined in the subgroups cid + AA and idio + AA and proteinuria dropped in the subgroups auto + AA and idio + AA.
- bDMARDs prevented progression to end-stage renal disease (ESRD) in 75% of the patients in the overall cohort, with progression to ESRD being prevented in 60% of patients with cid + AA, 88% of patients with auto + AA, and 81% of patients with idio + AA.
- Tocilizumab was more effective than other bDMARDs in preventing renal progression to ESRD (P = .0006), with a similar pattern observed for the subgroups cid + AA (P = .0126) and idio + AA (P = .0259).
- None of the patients receiving tocilizumab died during the nearly 5-year follow-up period.
IN PRACTICE:
“The data suggest preferential use of IL [interleukin]-1 inhibitors and tocilizumab for clinical use in the treatment of AA amyloidosis depending on the respective underlying diseases,” the authors wrote.
SOURCE:
This study, led by Peter Kvacskay, MD, of Heidelberg University Hospital, Heidelberg, Germany, was published online on April 23 in Annals of the Rheumatic Diseases.
LIMITATIONS:
Authors acknowledged the retrospective nature of the analysis and missing data of single patients during the long-term follow-up as major limitations. Furthermore, the cid + AA subgroup was heterogeneous in terms of the pathophysiology of their underlying primary disease.
DISCLOSURES:
This study did not report any source of funding. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Treatment with biologic disease-modifying antirheumatic drugs (bDMARDs), particularly tocilizumab, can suppress inflammation and preserve renal function in a majority of patients with chronic inflammatory disorders who develop serum amyloid alpha (SAA) amyloidosis.
METHODOLOGY:
- AA amyloidosis, characterized by the misfolding of the SAA protein, is observed in patients with inflammatory diseases and can lead to progressive organ damage, including chronic kidney disease, malabsorption with cachexia, and cardiac failure.
- This monocentric, retrospective analysis assessed the effect of bDMARD therapy on inflammatory biomarker levels and renal outcomes in 83 patients with AA amyloidosis who were followed for a mean period of 4.82 years.
- The patients were stratified into three major subgroups depending on the cause of AA amyloidosis:
- Chronic inflammatory diseases (cid + AA; n = 34) such as rheumatoid arthritis, Crohn’s disease, and chronic infections
- Autoinflammatory syndromes (auto + AA; n = 24) such as familial Mediterranean fever (FMF) and cryopyrin-associated periodic syndrome (CAPS)
- Idiopathic AA (idio + AA; n = 25), wherein the primary disease could not be identified
- Tocilizumab was the most commonly used bDMARD in patients with cid + AA and idio + AA amyloidosis, and interleukin-1 inhibitors were prescribed to patients with auto + AA amyloidosis because tocilizumab has not been approved yet for FMF or CAPS treatment.
- All patients with AA amyloidosis had renal involvement, as confirmed by kidney biopsy.
TAKEAWAY:
- After bDMARD therapy, C-reactive protein levels reduced significantly from baseline to the last-documented visit in all subgroups, while SAA levels declined in the subgroups cid + AA and idio + AA and proteinuria dropped in the subgroups auto + AA and idio + AA.
- bDMARDs prevented progression to end-stage renal disease (ESRD) in 75% of the patients in the overall cohort, with progression to ESRD being prevented in 60% of patients with cid + AA, 88% of patients with auto + AA, and 81% of patients with idio + AA.
- Tocilizumab was more effective than other bDMARDs in preventing renal progression to ESRD (P = .0006), with a similar pattern observed for the subgroups cid + AA (P = .0126) and idio + AA (P = .0259).
- None of the patients receiving tocilizumab died during the nearly 5-year follow-up period.
IN PRACTICE:
“The data suggest preferential use of IL [interleukin]-1 inhibitors and tocilizumab for clinical use in the treatment of AA amyloidosis depending on the respective underlying diseases,” the authors wrote.
SOURCE:
This study, led by Peter Kvacskay, MD, of Heidelberg University Hospital, Heidelberg, Germany, was published online on April 23 in Annals of the Rheumatic Diseases.
LIMITATIONS:
Authors acknowledged the retrospective nature of the analysis and missing data of single patients during the long-term follow-up as major limitations. Furthermore, the cid + AA subgroup was heterogeneous in terms of the pathophysiology of their underlying primary disease.
DISCLOSURES:
This study did not report any source of funding. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Treatment with biologic disease-modifying antirheumatic drugs (bDMARDs), particularly tocilizumab, can suppress inflammation and preserve renal function in a majority of patients with chronic inflammatory disorders who develop serum amyloid alpha (SAA) amyloidosis.
METHODOLOGY:
- AA amyloidosis, characterized by the misfolding of the SAA protein, is observed in patients with inflammatory diseases and can lead to progressive organ damage, including chronic kidney disease, malabsorption with cachexia, and cardiac failure.
- This monocentric, retrospective analysis assessed the effect of bDMARD therapy on inflammatory biomarker levels and renal outcomes in 83 patients with AA amyloidosis who were followed for a mean period of 4.82 years.
- The patients were stratified into three major subgroups depending on the cause of AA amyloidosis:
- Chronic inflammatory diseases (cid + AA; n = 34) such as rheumatoid arthritis, Crohn’s disease, and chronic infections
- Autoinflammatory syndromes (auto + AA; n = 24) such as familial Mediterranean fever (FMF) and cryopyrin-associated periodic syndrome (CAPS)
- Idiopathic AA (idio + AA; n = 25), wherein the primary disease could not be identified
- Tocilizumab was the most commonly used bDMARD in patients with cid + AA and idio + AA amyloidosis, and interleukin-1 inhibitors were prescribed to patients with auto + AA amyloidosis because tocilizumab has not been approved yet for FMF or CAPS treatment.
- All patients with AA amyloidosis had renal involvement, as confirmed by kidney biopsy.
TAKEAWAY:
- After bDMARD therapy, C-reactive protein levels reduced significantly from baseline to the last-documented visit in all subgroups, while SAA levels declined in the subgroups cid + AA and idio + AA and proteinuria dropped in the subgroups auto + AA and idio + AA.
- bDMARDs prevented progression to end-stage renal disease (ESRD) in 75% of the patients in the overall cohort, with progression to ESRD being prevented in 60% of patients with cid + AA, 88% of patients with auto + AA, and 81% of patients with idio + AA.
- Tocilizumab was more effective than other bDMARDs in preventing renal progression to ESRD (P = .0006), with a similar pattern observed for the subgroups cid + AA (P = .0126) and idio + AA (P = .0259).
- None of the patients receiving tocilizumab died during the nearly 5-year follow-up period.
IN PRACTICE:
“The data suggest preferential use of IL [interleukin]-1 inhibitors and tocilizumab for clinical use in the treatment of AA amyloidosis depending on the respective underlying diseases,” the authors wrote.
SOURCE:
This study, led by Peter Kvacskay, MD, of Heidelberg University Hospital, Heidelberg, Germany, was published online on April 23 in Annals of the Rheumatic Diseases.
LIMITATIONS:
Authors acknowledged the retrospective nature of the analysis and missing data of single patients during the long-term follow-up as major limitations. Furthermore, the cid + AA subgroup was heterogeneous in terms of the pathophysiology of their underlying primary disease.
DISCLOSURES:
This study did not report any source of funding. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Second Primary BC Risk Low in Young BC Survivors Without Germline Mutations
Key clinical point: Young breast cancer (BC) survivors with a germline pathogenic variant had a higher risk for second primary breast cancer (SPBC) in the first 10 years after diagnosis than those without any mutation.
Major finding: Over a median follow-up of 10 years, 2.5% of BC survivors developed an SPBC. The SPBC risk was around five times higher in carriers vs noncarriers of germline pathogenic variants (subdistribution hazard ratio [sHR] 5.27; P = .01) and in women with primary in situ vs invasive BC (10.4% vs 2.1%; sHR 5.61; P = .01).
Study details: This prospective cohort study included 685 women diagnosed with stages 0-III BC at age ≤ 40 years who underwent unilateral mastectomy or lumpectomy as the primary surgery.
Disclosures: This study was funded by Susan G. Komen and the Breast Cancer Research Foundation. Four authors declared receiving grants or author royalties from various sources.
Source: Brantley KD, Rosenberg SM, Collins LC, et al. Second primary breast cancer in young breast cancer survivors. JAMA Oncol. 2024 (Apr 11). doi: 10.1001/jamaoncol.2024.0286 Source
Key clinical point: Young breast cancer (BC) survivors with a germline pathogenic variant had a higher risk for second primary breast cancer (SPBC) in the first 10 years after diagnosis than those without any mutation.
Major finding: Over a median follow-up of 10 years, 2.5% of BC survivors developed an SPBC. The SPBC risk was around five times higher in carriers vs noncarriers of germline pathogenic variants (subdistribution hazard ratio [sHR] 5.27; P = .01) and in women with primary in situ vs invasive BC (10.4% vs 2.1%; sHR 5.61; P = .01).
Study details: This prospective cohort study included 685 women diagnosed with stages 0-III BC at age ≤ 40 years who underwent unilateral mastectomy or lumpectomy as the primary surgery.
Disclosures: This study was funded by Susan G. Komen and the Breast Cancer Research Foundation. Four authors declared receiving grants or author royalties from various sources.
Source: Brantley KD, Rosenberg SM, Collins LC, et al. Second primary breast cancer in young breast cancer survivors. JAMA Oncol. 2024 (Apr 11). doi: 10.1001/jamaoncol.2024.0286 Source
Key clinical point: Young breast cancer (BC) survivors with a germline pathogenic variant had a higher risk for second primary breast cancer (SPBC) in the first 10 years after diagnosis than those without any mutation.
Major finding: Over a median follow-up of 10 years, 2.5% of BC survivors developed an SPBC. The SPBC risk was around five times higher in carriers vs noncarriers of germline pathogenic variants (subdistribution hazard ratio [sHR] 5.27; P = .01) and in women with primary in situ vs invasive BC (10.4% vs 2.1%; sHR 5.61; P = .01).
Study details: This prospective cohort study included 685 women diagnosed with stages 0-III BC at age ≤ 40 years who underwent unilateral mastectomy or lumpectomy as the primary surgery.
Disclosures: This study was funded by Susan G. Komen and the Breast Cancer Research Foundation. Four authors declared receiving grants or author royalties from various sources.
Source: Brantley KD, Rosenberg SM, Collins LC, et al. Second primary breast cancer in young breast cancer survivors. JAMA Oncol. 2024 (Apr 11). doi: 10.1001/jamaoncol.2024.0286 Source
Aspirin Is Not a Suitable Adjuvant Breast Cancer Treatment
Key clinical point: A once-daily dose of 300 mg aspirin in the adjuvant setting did not reduce risk for breast cancer (BC) recurrence or improve survival outcomes as compared with placebo in patients with high-risk nonmetastatic BC.
Major finding: Treatment with aspirin and placebo led to comparable invasive disease-free survival (hazard ratio [HR] 1.27; P = .06) and overall survival outcomes (HR 1.19; P = .36) along with similar rates of grades 3 and 4 adverse events.
Study details: This phase 3 trial included 3020 patients with high-risk nonmetastatic BC (age 18 to <70 years) and a history of human epidermal growth factor receptor 2-negative BC who were treated with standard therapy and were randomly assigned to receive 300 mg aspirin or placebo once daily.
Disclosures: This study was supported by the US Department of Defense Breast Cancer Research Program and other sources. Five authors declared receiving grants, royalties, or consulting fees from various sources.
Source: Chen WY, Ballman KV, Partridge AH, et al. Aspirin vs placebo as adjuvant therapy for breast cancer: The Alliance A011502 randomized trial. JAMA. 2024 (Apr 29). doi: 10.1001/jama.2024.4840 Source
Key clinical point: A once-daily dose of 300 mg aspirin in the adjuvant setting did not reduce risk for breast cancer (BC) recurrence or improve survival outcomes as compared with placebo in patients with high-risk nonmetastatic BC.
Major finding: Treatment with aspirin and placebo led to comparable invasive disease-free survival (hazard ratio [HR] 1.27; P = .06) and overall survival outcomes (HR 1.19; P = .36) along with similar rates of grades 3 and 4 adverse events.
Study details: This phase 3 trial included 3020 patients with high-risk nonmetastatic BC (age 18 to <70 years) and a history of human epidermal growth factor receptor 2-negative BC who were treated with standard therapy and were randomly assigned to receive 300 mg aspirin or placebo once daily.
Disclosures: This study was supported by the US Department of Defense Breast Cancer Research Program and other sources. Five authors declared receiving grants, royalties, or consulting fees from various sources.
Source: Chen WY, Ballman KV, Partridge AH, et al. Aspirin vs placebo as adjuvant therapy for breast cancer: The Alliance A011502 randomized trial. JAMA. 2024 (Apr 29). doi: 10.1001/jama.2024.4840 Source
Key clinical point: A once-daily dose of 300 mg aspirin in the adjuvant setting did not reduce risk for breast cancer (BC) recurrence or improve survival outcomes as compared with placebo in patients with high-risk nonmetastatic BC.
Major finding: Treatment with aspirin and placebo led to comparable invasive disease-free survival (hazard ratio [HR] 1.27; P = .06) and overall survival outcomes (HR 1.19; P = .36) along with similar rates of grades 3 and 4 adverse events.
Study details: This phase 3 trial included 3020 patients with high-risk nonmetastatic BC (age 18 to <70 years) and a history of human epidermal growth factor receptor 2-negative BC who were treated with standard therapy and were randomly assigned to receive 300 mg aspirin or placebo once daily.
Disclosures: This study was supported by the US Department of Defense Breast Cancer Research Program and other sources. Five authors declared receiving grants, royalties, or consulting fees from various sources.
Source: Chen WY, Ballman KV, Partridge AH, et al. Aspirin vs placebo as adjuvant therapy for breast cancer: The Alliance A011502 randomized trial. JAMA. 2024 (Apr 29). doi: 10.1001/jama.2024.4840 Source