Clinical Edge Journal Scan

Key clinical point: A mutation load of the gene U2AF1 (VAF > 40%) was an independent indicator of lower 1-year survival in adults with myelodysplastic syndrome.

Major finding: Myelodysplastic syndrome patients with a higher mutation load of U2AF1 (VAF > 40%) had a significantly lower 1-year survival rate compared to those with a mutation load of VAF 40 or lower (46.1% and 80.5%, respectively, P= 0.027). 

Study details: The data come from genetic analyses of 234 myelodysplastic syndrome patients aged 17 to 86 years; a total of 51 patients had an U2AF1 mutation at 52 mutation sites. 

Disclosures: The study was supported by the National Natural Science Foundation of China; Henan Natural Science Foundation of China and by the Henan Medical Science and Technology Research Project, Key Scientific Research Project of Henan Provincial Education Department. The researchers had no financial conflicts to disclose.

Source: Wang H et al. Sci Rep. 2020 Oct 29. doi: 10.1038/s41598-020-74744-z.

Key clinical point: A mutation load of the gene U2AF1 (VAF > 40%) was an independent indicator of lower 1-year survival in adults with myelodysplastic syndrome.

Major finding: Myelodysplastic syndrome patients with a higher mutation load of U2AF1 (VAF > 40%) had a significantly lower 1-year survival rate compared to those with a mutation load of VAF 40 or lower (46.1% and 80.5%, respectively, P= 0.027). 

Study details: The data come from genetic analyses of 234 myelodysplastic syndrome patients aged 17 to 86 years; a total of 51 patients had an U2AF1 mutation at 52 mutation sites. 

Disclosures: The study was supported by the National Natural Science Foundation of China; Henan Natural Science Foundation of China and by the Henan Medical Science and Technology Research Project, Key Scientific Research Project of Henan Provincial Education Department. The researchers had no financial conflicts to disclose.

Source: Wang H et al. Sci Rep. 2020 Oct 29. doi: 10.1038/s41598-020-74744-z.

Key clinical point: A mutation load of the gene U2AF1 (VAF > 40%) was an independent indicator of lower 1-year survival in adults with myelodysplastic syndrome.

Major finding: Myelodysplastic syndrome patients with a higher mutation load of U2AF1 (VAF > 40%) had a significantly lower 1-year survival rate compared to those with a mutation load of VAF 40 or lower (46.1% and 80.5%, respectively, P= 0.027). 

Study details: The data come from genetic analyses of 234 myelodysplastic syndrome patients aged 17 to 86 years; a total of 51 patients had an U2AF1 mutation at 52 mutation sites. 

Disclosures: The study was supported by the National Natural Science Foundation of China; Henan Natural Science Foundation of China and by the Henan Medical Science and Technology Research Project, Key Scientific Research Project of Henan Provincial Education Department. The researchers had no financial conflicts to disclose.

Source: Wang H et al. Sci Rep. 2020 Oct 29. doi: 10.1038/s41598-020-74744-z.

Key clinical point: Novel gene fusions may have a role in developing biomarkers for monitoring of minimal residual disease (MRD) in patients with acute myeloid leukemia and myelodysplastic syndrome.

Major finding: Overall, gene fusion events occurred in 37% of patients with acute myeloid leukemia compared to 3% of those with myelodysplastic syndrome. In addition, 67% of AML patients had TB53 mutations and 71% had complex karyotypes, compared with 26% and 21%, respectively, of MDS patients.

Study details: The data come from a review of gene transcripts from 572 adults with acute myeloid leukemia and 630 with myelodysplastic syndrome.

Disclosures: The study received no outside funding. Lead author Dr. Stengel had no financial conflicts to disclose.

Source: Stengel A et al. Blood Adv. 2020 Nov 10. doi: 10.1182/bloodadvances.2020003007.

Key clinical point: Novel gene fusions may have a role in developing biomarkers for monitoring of minimal residual disease (MRD) in patients with acute myeloid leukemia and myelodysplastic syndrome.

Major finding: Overall, gene fusion events occurred in 37% of patients with acute myeloid leukemia compared to 3% of those with myelodysplastic syndrome. In addition, 67% of AML patients had TB53 mutations and 71% had complex karyotypes, compared with 26% and 21%, respectively, of MDS patients.

Study details: The data come from a review of gene transcripts from 572 adults with acute myeloid leukemia and 630 with myelodysplastic syndrome.

Disclosures: The study received no outside funding. Lead author Dr. Stengel had no financial conflicts to disclose.

Source: Stengel A et al. Blood Adv. 2020 Nov 10. doi: 10.1182/bloodadvances.2020003007.

Key clinical point: Novel gene fusions may have a role in developing biomarkers for monitoring of minimal residual disease (MRD) in patients with acute myeloid leukemia and myelodysplastic syndrome.

Major finding: Overall, gene fusion events occurred in 37% of patients with acute myeloid leukemia compared to 3% of those with myelodysplastic syndrome. In addition, 67% of AML patients had TB53 mutations and 71% had complex karyotypes, compared with 26% and 21%, respectively, of MDS patients.

Study details: The data come from a review of gene transcripts from 572 adults with acute myeloid leukemia and 630 with myelodysplastic syndrome.

Disclosures: The study received no outside funding. Lead author Dr. Stengel had no financial conflicts to disclose.

Source: Stengel A et al. Blood Adv. 2020 Nov 10. doi: 10.1182/bloodadvances.2020003007.

Key clinical point: Azacitidine was safe but had no significant impact on relapse-free survival after transplant in in patients with acute myeloid leukemia/myelodysplastic syndrome 

Major finding: Median relapse-free survival (RFS) was 2.07 years in the azacitidine group vs. 1.28 years in the control group (P = .19). 

Study details: The data come from a phase 3 open-label randomized trial of 187 patients aged 18 to 75 years with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS); patients received 32 mg/m2 of azacitidine daily for 5 days every 28 days for 12 cycles.

Disclosures: The study was supported by Celgene Pharmaceuticals. Lead author Dr. Oran disclosed serving as a consultant for Celgene and receiving research funding from AROG Pharmaceuticals and Astex Pharmaceuticals.

Source: Oran B et al. Blood Adv. 2020 Nov 10. doi: 10.1182/bloodadvances.2020002544.

Key clinical point: Azacitidine was safe but had no significant impact on relapse-free survival after transplant in in patients with acute myeloid leukemia/myelodysplastic syndrome 

Major finding: Median relapse-free survival (RFS) was 2.07 years in the azacitidine group vs. 1.28 years in the control group (P = .19). 

Study details: The data come from a phase 3 open-label randomized trial of 187 patients aged 18 to 75 years with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS); patients received 32 mg/m2 of azacitidine daily for 5 days every 28 days for 12 cycles.

Disclosures: The study was supported by Celgene Pharmaceuticals. Lead author Dr. Oran disclosed serving as a consultant for Celgene and receiving research funding from AROG Pharmaceuticals and Astex Pharmaceuticals.

Source: Oran B et al. Blood Adv. 2020 Nov 10. doi: 10.1182/bloodadvances.2020002544.

Key clinical point: Azacitidine was safe but had no significant impact on relapse-free survival after transplant in in patients with acute myeloid leukemia/myelodysplastic syndrome 

Major finding: Median relapse-free survival (RFS) was 2.07 years in the azacitidine group vs. 1.28 years in the control group (P = .19). 

Study details: The data come from a phase 3 open-label randomized trial of 187 patients aged 18 to 75 years with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS); patients received 32 mg/m2 of azacitidine daily for 5 days every 28 days for 12 cycles.

Disclosures: The study was supported by Celgene Pharmaceuticals. Lead author Dr. Oran disclosed serving as a consultant for Celgene and receiving research funding from AROG Pharmaceuticals and Astex Pharmaceuticals.

Source: Oran B et al. Blood Adv. 2020 Nov 10. doi: 10.1182/bloodadvances.2020002544.

Key clinical point: Imetelstat increased transfusion independence for patients with lower risk myelodysplastic syndromes who were resistant or refractory to treatment with erythropoiesis-stimulating agent.

Major finding: At 8 weeks, 37% of the patients were red blood cell transfusion independent, with an average duration of 65 weeks.

Study details: The data come from a phase II study of 57 adult patients with lower-risk myelodysplastic syndromes dependent on red blood cell transfusion and relapsed or refractory to erythropoiesis-stimulating agent; patients received imetelstat with a primary endpoint of red blood cell transfusion independence at 8 weeks.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Steensma DP et al. J Clin Oncol. 2020 Oct 27. doi: 10.1200/JCO.20.01895. 

Key clinical point: Imetelstat increased transfusion independence for patients with lower risk myelodysplastic syndromes who were resistant or refractory to treatment with erythropoiesis-stimulating agent.

Major finding: At 8 weeks, 37% of the patients were red blood cell transfusion independent, with an average duration of 65 weeks.

Study details: The data come from a phase II study of 57 adult patients with lower-risk myelodysplastic syndromes dependent on red blood cell transfusion and relapsed or refractory to erythropoiesis-stimulating agent; patients received imetelstat with a primary endpoint of red blood cell transfusion independence at 8 weeks.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Steensma DP et al. J Clin Oncol. 2020 Oct 27. doi: 10.1200/JCO.20.01895. 

Key clinical point: Imetelstat increased transfusion independence for patients with lower risk myelodysplastic syndromes who were resistant or refractory to treatment with erythropoiesis-stimulating agent.

Major finding: At 8 weeks, 37% of the patients were red blood cell transfusion independent, with an average duration of 65 weeks.

Study details: The data come from a phase II study of 57 adult patients with lower-risk myelodysplastic syndromes dependent on red blood cell transfusion and relapsed or refractory to erythropoiesis-stimulating agent; patients received imetelstat with a primary endpoint of red blood cell transfusion independence at 8 weeks.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Steensma DP et al. J Clin Oncol. 2020 Oct 27. doi: 10.1200/JCO.20.01895. 

Key clinical point: Food supplements coenzyme Q10 and carnitine significantly improved mitochondrial respiration in patients with low-risk myelodysplastic syndrome

Major finding: A total of 6 patients (21.4%) achieved hematological improvement based on the International Working Group (IWG) response criteria for MDS after 6 months.

Study details: The data come from an open-label study of 33 adults with myelodysplastic syndrome aged 56 to 93 years who received a combination of coenzyme Q10 at 180 mg/day L-carnitine at 2000 mg/ day, and a standard vitamin-mineral complex daily.

Disclosures: The study was supported by the Rising Tide Foundation and Israel Society of Hematology and Blood Transfusion. The researchers had no financial conflicts to disclose.

Source: Filanovsky K et al. Mediterr J Hemtol Infec Dis. 2020 Nov 1. doi: 10.4084/MJHID.2020.072.

Key clinical point: Food supplements coenzyme Q10 and carnitine significantly improved mitochondrial respiration in patients with low-risk myelodysplastic syndrome

Major finding: A total of 6 patients (21.4%) achieved hematological improvement based on the International Working Group (IWG) response criteria for MDS after 6 months.

Study details: The data come from an open-label study of 33 adults with myelodysplastic syndrome aged 56 to 93 years who received a combination of coenzyme Q10 at 180 mg/day L-carnitine at 2000 mg/ day, and a standard vitamin-mineral complex daily.

Disclosures: The study was supported by the Rising Tide Foundation and Israel Society of Hematology and Blood Transfusion. The researchers had no financial conflicts to disclose.

Source: Filanovsky K et al. Mediterr J Hemtol Infec Dis. 2020 Nov 1. doi: 10.4084/MJHID.2020.072.

Key clinical point: Food supplements coenzyme Q10 and carnitine significantly improved mitochondrial respiration in patients with low-risk myelodysplastic syndrome

Major finding: A total of 6 patients (21.4%) achieved hematological improvement based on the International Working Group (IWG) response criteria for MDS after 6 months.

Study details: The data come from an open-label study of 33 adults with myelodysplastic syndrome aged 56 to 93 years who received a combination of coenzyme Q10 at 180 mg/day L-carnitine at 2000 mg/ day, and a standard vitamin-mineral complex daily.

Disclosures: The study was supported by the Rising Tide Foundation and Israel Society of Hematology and Blood Transfusion. The researchers had no financial conflicts to disclose.

Source: Filanovsky K et al. Mediterr J Hemtol Infec Dis. 2020 Nov 1. doi: 10.4084/MJHID.2020.072.

Key clinical point: The financial burden of monthly azacitidine must be weighed against the benefits of treatment, but patients with acute myeloid leukemia and myelodysplastic syndrome have few options.

Major finding: A total of 31 patients with measurable residual disease at baseline were relapse-free and alive after 6 months of monthly injection treatment with azacitidine.

Study details: The data come from a review of the pros and cons of the RELAZA-2, a German-multicentered, open-label, single-arm, phase II study of azacitidine in 53 adult patients who developed measurable residual disease after treatment for acute myeloid leukemia or advanced myelodysplastic syndrome; 29 after chemotherapy and 24 after allogeneic hematopoietic stem cell transplantation (ASCT).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Pan J et al. Front Oncol. 2020 Oct 22. doi: 10.3389/fonc.2020.576924.

Key clinical point: The financial burden of monthly azacitidine must be weighed against the benefits of treatment, but patients with acute myeloid leukemia and myelodysplastic syndrome have few options.

Major finding: A total of 31 patients with measurable residual disease at baseline were relapse-free and alive after 6 months of monthly injection treatment with azacitidine.

Study details: The data come from a review of the pros and cons of the RELAZA-2, a German-multicentered, open-label, single-arm, phase II study of azacitidine in 53 adult patients who developed measurable residual disease after treatment for acute myeloid leukemia or advanced myelodysplastic syndrome; 29 after chemotherapy and 24 after allogeneic hematopoietic stem cell transplantation (ASCT).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Pan J et al. Front Oncol. 2020 Oct 22. doi: 10.3389/fonc.2020.576924.

Key clinical point: The financial burden of monthly azacitidine must be weighed against the benefits of treatment, but patients with acute myeloid leukemia and myelodysplastic syndrome have few options.

Major finding: A total of 31 patients with measurable residual disease at baseline were relapse-free and alive after 6 months of monthly injection treatment with azacitidine.

Study details: The data come from a review of the pros and cons of the RELAZA-2, a German-multicentered, open-label, single-arm, phase II study of azacitidine in 53 adult patients who developed measurable residual disease after treatment for acute myeloid leukemia or advanced myelodysplastic syndrome; 29 after chemotherapy and 24 after allogeneic hematopoietic stem cell transplantation (ASCT).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Pan J et al. Front Oncol. 2020 Oct 22. doi: 10.3389/fonc.2020.576924.

Key clinical point: A novel retinoic acid receptor alpha agonist appeared safe in a phase 1 study of patients with relapsed and refractory high-grade myelodysplastic syndrome or acute myelogenous leukemia.

Major finding: A total of 4 of 11 patients (36%) had stable disease or better after two 28-day treatment cycles; the study ended early because of an inadequate supply of the drug.

Study details: The data come from a phase 1 dose-escalation study of the novel retinoic acid receptor alpha agonist IRX195183; 11 adults aged 18 to 60 years with relapsed or refractory myelodysplastic syndrome or acute myelogenous leukemia received the drug for two 28-day cycles with dosage starting at 50 mg daily or 75 mg daily.

Disclosures: The study was supported by the National Heart, Lung, and Blood Institute, the National Cancer Institute, the Leukemia and Lymphoma Society, and the Augustine Fellowship. IRX195183 was provided by Io Therapeutics, Inc. Lead author Dr. Ambinder had no financial conflicts to disclose. Several coauthors are authors on a patent for the use of IRX195183.

Source: Ambinder AJ et al. Front Oncol. 2020 Oct 23. doi: 10.3389/fonc.2020.587062.

Key clinical point: A novel retinoic acid receptor alpha agonist appeared safe in a phase 1 study of patients with relapsed and refractory high-grade myelodysplastic syndrome or acute myelogenous leukemia.

Major finding: A total of 4 of 11 patients (36%) had stable disease or better after two 28-day treatment cycles; the study ended early because of an inadequate supply of the drug.

Study details: The data come from a phase 1 dose-escalation study of the novel retinoic acid receptor alpha agonist IRX195183; 11 adults aged 18 to 60 years with relapsed or refractory myelodysplastic syndrome or acute myelogenous leukemia received the drug for two 28-day cycles with dosage starting at 50 mg daily or 75 mg daily.

Disclosures: The study was supported by the National Heart, Lung, and Blood Institute, the National Cancer Institute, the Leukemia and Lymphoma Society, and the Augustine Fellowship. IRX195183 was provided by Io Therapeutics, Inc. Lead author Dr. Ambinder had no financial conflicts to disclose. Several coauthors are authors on a patent for the use of IRX195183.

Source: Ambinder AJ et al. Front Oncol. 2020 Oct 23. doi: 10.3389/fonc.2020.587062.

Key clinical point: A novel retinoic acid receptor alpha agonist appeared safe in a phase 1 study of patients with relapsed and refractory high-grade myelodysplastic syndrome or acute myelogenous leukemia.

Major finding: A total of 4 of 11 patients (36%) had stable disease or better after two 28-day treatment cycles; the study ended early because of an inadequate supply of the drug.

Study details: The data come from a phase 1 dose-escalation study of the novel retinoic acid receptor alpha agonist IRX195183; 11 adults aged 18 to 60 years with relapsed or refractory myelodysplastic syndrome or acute myelogenous leukemia received the drug for two 28-day cycles with dosage starting at 50 mg daily or 75 mg daily.

Disclosures: The study was supported by the National Heart, Lung, and Blood Institute, the National Cancer Institute, the Leukemia and Lymphoma Society, and the Augustine Fellowship. IRX195183 was provided by Io Therapeutics, Inc. Lead author Dr. Ambinder had no financial conflicts to disclose. Several coauthors are authors on a patent for the use of IRX195183.

Source: Ambinder AJ et al. Front Oncol. 2020 Oct 23. doi: 10.3389/fonc.2020.587062.

The utilization of neoadjuvant chemotherapy is increasing, and is considered standard of care for the majority of patients with HER2-positive and triple-negative breast cancer subtypes. A significant benefit of neoadjuvant systemic therapy is assessment of the tumor biology via chemotherapy response, which has prognostic implications and additionally can help tailor therapy in the adjuvant setting. In the era of precision medicine, de-escalation strategies are considered to provide patients with efficacious treatment and spare toxicity. Tasoulis et al assessed the accuracy of image-guided biopsy after neoadjuvant therapy to predict residual disease, and found a false negative rate (FNR) of 3.2% and negative predictive value (NPV) of 97.4% when the residual imaging abnormality was 2cm or smaller with a minimum of 6 vacuum-assisted biopsies performed. They also demonstrated a FNR of 4.2% and NPV of 97.2% in the subgroup of patients with ERBB2-positive and triple-negative subtypes, those most likely to achieve a pathologic complete response. These findings suggest that local therapy de-escalation may be a relevant strategy for those patients who have excellent responses to neoadjuvant chemotherapy.

Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) have historically been, and still are, considered important prognostic and predictive factors. Beyond these, the role of genomic assays in breast cancer is evolving, and the 21-gene recurrence score is a valuable prognostic tool to assess chemotherapy benefit in women with early-stage ER-positive, HER2-negative breast cancer. Precision medicine in oncology strives to identify and apply an individualized approach to cancer care based on strong scientific data. Zhang and colleagues demonstrated the prognostic ability of an 8 DNA repair-related gene signature that was constructed from gene expression profiles from over 1,000 women diagnosed with breast cancer. These genes have roles in ER-mediated transactivation, DNA damage repair and cell adhesion processes. Additionally, Kudela et al showed that microRNAs (mRNAs), which are small RNAs that regulate gene expression, are able to classify intrinsic breast cancer subtype, play a role in endocrine resistance, and may also enhance the function of predictive models such as the 21-gene recurrence score (Kudela). Ongoing research in the field of tumor genomics will help advance the field of personalized treatment for breast cancer.

Erin Roesch, MD
The Cleveland Clinic

References:

Killelea BK, Yang VQ, Wang SY, Hayse B, Mougalian S, Horowitz NR, Chagpar AB, Pusztai L, Lannin DR. Racial differences in the use and outcome of neoadjuvant chemotherapy for breast cancer: results from the National Cancer Data Base. J Clin Oncol. 2015;33:4267-76.

Heil J, Schaefgen B, Sinn P, Harcos A, Gomez C, Stieber A, Hennings A, Schuetz F, Sohn C, Schneeweiss A, Golatta M. Diagnosis of pathological complete response to neoadjuvant chemotherapy in breast cancer by minimal invasive biopsy techniques. Br J Cancer. 2015;113:1565-70.

Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Goetz MP, Olson JA Jr, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin PM, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge GW Jr. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379:111-21.

Emmadi R, Canestrari E, Arbieva ZH, Mu W, Dai Y, Frasor J, Wiley E. Correlative analysis of miRNA expression and Oncotype Dx Recurrence Score in estrogen receptor positive breast carcinomas. PLoS One. 2015;10:e0145346.

The utilization of neoadjuvant chemotherapy is increasing, and is considered standard of care for the majority of patients with HER2-positive and triple-negative breast cancer subtypes. A significant benefit of neoadjuvant systemic therapy is assessment of the tumor biology via chemotherapy response, which has prognostic implications and additionally can help tailor therapy in the adjuvant setting. In the era of precision medicine, de-escalation strategies are considered to provide patients with efficacious treatment and spare toxicity. Tasoulis et al assessed the accuracy of image-guided biopsy after neoadjuvant therapy to predict residual disease, and found a false negative rate (FNR) of 3.2% and negative predictive value (NPV) of 97.4% when the residual imaging abnormality was 2cm or smaller with a minimum of 6 vacuum-assisted biopsies performed. They also demonstrated a FNR of 4.2% and NPV of 97.2% in the subgroup of patients with ERBB2-positive and triple-negative subtypes, those most likely to achieve a pathologic complete response. These findings suggest that local therapy de-escalation may be a relevant strategy for those patients who have excellent responses to neoadjuvant chemotherapy.

Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) have historically been, and still are, considered important prognostic and predictive factors. Beyond these, the role of genomic assays in breast cancer is evolving, and the 21-gene recurrence score is a valuable prognostic tool to assess chemotherapy benefit in women with early-stage ER-positive, HER2-negative breast cancer. Precision medicine in oncology strives to identify and apply an individualized approach to cancer care based on strong scientific data. Zhang and colleagues demonstrated the prognostic ability of an 8 DNA repair-related gene signature that was constructed from gene expression profiles from over 1,000 women diagnosed with breast cancer. These genes have roles in ER-mediated transactivation, DNA damage repair and cell adhesion processes. Additionally, Kudela et al showed that microRNAs (mRNAs), which are small RNAs that regulate gene expression, are able to classify intrinsic breast cancer subtype, play a role in endocrine resistance, and may also enhance the function of predictive models such as the 21-gene recurrence score (Kudela). Ongoing research in the field of tumor genomics will help advance the field of personalized treatment for breast cancer.

Erin Roesch, MD
The Cleveland Clinic

References:

Killelea BK, Yang VQ, Wang SY, Hayse B, Mougalian S, Horowitz NR, Chagpar AB, Pusztai L, Lannin DR. Racial differences in the use and outcome of neoadjuvant chemotherapy for breast cancer: results from the National Cancer Data Base. J Clin Oncol. 2015;33:4267-76.

Heil J, Schaefgen B, Sinn P, Harcos A, Gomez C, Stieber A, Hennings A, Schuetz F, Sohn C, Schneeweiss A, Golatta M. Diagnosis of pathological complete response to neoadjuvant chemotherapy in breast cancer by minimal invasive biopsy techniques. Br J Cancer. 2015;113:1565-70.

Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Goetz MP, Olson JA Jr, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin PM, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge GW Jr. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379:111-21.

Emmadi R, Canestrari E, Arbieva ZH, Mu W, Dai Y, Frasor J, Wiley E. Correlative analysis of miRNA expression and Oncotype Dx Recurrence Score in estrogen receptor positive breast carcinomas. PLoS One. 2015;10:e0145346.

The utilization of neoadjuvant chemotherapy is increasing, and is considered standard of care for the majority of patients with HER2-positive and triple-negative breast cancer subtypes. A significant benefit of neoadjuvant systemic therapy is assessment of the tumor biology via chemotherapy response, which has prognostic implications and additionally can help tailor therapy in the adjuvant setting. In the era of precision medicine, de-escalation strategies are considered to provide patients with efficacious treatment and spare toxicity. Tasoulis et al assessed the accuracy of image-guided biopsy after neoadjuvant therapy to predict residual disease, and found a false negative rate (FNR) of 3.2% and negative predictive value (NPV) of 97.4% when the residual imaging abnormality was 2cm or smaller with a minimum of 6 vacuum-assisted biopsies performed. They also demonstrated a FNR of 4.2% and NPV of 97.2% in the subgroup of patients with ERBB2-positive and triple-negative subtypes, those most likely to achieve a pathologic complete response. These findings suggest that local therapy de-escalation may be a relevant strategy for those patients who have excellent responses to neoadjuvant chemotherapy.

Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) have historically been, and still are, considered important prognostic and predictive factors. Beyond these, the role of genomic assays in breast cancer is evolving, and the 21-gene recurrence score is a valuable prognostic tool to assess chemotherapy benefit in women with early-stage ER-positive, HER2-negative breast cancer. Precision medicine in oncology strives to identify and apply an individualized approach to cancer care based on strong scientific data. Zhang and colleagues demonstrated the prognostic ability of an 8 DNA repair-related gene signature that was constructed from gene expression profiles from over 1,000 women diagnosed with breast cancer. These genes have roles in ER-mediated transactivation, DNA damage repair and cell adhesion processes. Additionally, Kudela et al showed that microRNAs (mRNAs), which are small RNAs that regulate gene expression, are able to classify intrinsic breast cancer subtype, play a role in endocrine resistance, and may also enhance the function of predictive models such as the 21-gene recurrence score (Kudela). Ongoing research in the field of tumor genomics will help advance the field of personalized treatment for breast cancer.

Erin Roesch, MD
The Cleveland Clinic

References:

Killelea BK, Yang VQ, Wang SY, Hayse B, Mougalian S, Horowitz NR, Chagpar AB, Pusztai L, Lannin DR. Racial differences in the use and outcome of neoadjuvant chemotherapy for breast cancer: results from the National Cancer Data Base. J Clin Oncol. 2015;33:4267-76.

Heil J, Schaefgen B, Sinn P, Harcos A, Gomez C, Stieber A, Hennings A, Schuetz F, Sohn C, Schneeweiss A, Golatta M. Diagnosis of pathological complete response to neoadjuvant chemotherapy in breast cancer by minimal invasive biopsy techniques. Br J Cancer. 2015;113:1565-70.

Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Goetz MP, Olson JA Jr, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin PM, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge GW Jr. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379:111-21.

Emmadi R, Canestrari E, Arbieva ZH, Mu W, Dai Y, Frasor J, Wiley E. Correlative analysis of miRNA expression and Oncotype Dx Recurrence Score in estrogen receptor positive breast carcinomas. PLoS One. 2015;10:e0145346.

Key clinical point: Differences in microRNAs (mRNAs), a group of small RNAs that regulate gene expression, can be used to distinguish among breast cancer subtypes.

Major finding: Altered expression of microRNAs distinguished between cancer and healthy samples, and also identified breast cancer subtypes including HER2, Luminal A, Luminal B, and triple negative breast cancer, according to a retrospective study of 740 breast cancer cases included in the review.

Study details: The data come from a review of the latest research on the prognostic and predictive value of microRNAs in patients with luminal A breast cancer.

Disclosures: The study was supported by the Scientific Grant Agency of the Ministry of Education of the Slovak Republic, the Slovak Research and Development Agency, and the Operational Programme Research and Innovation funded by the ERDF.

Citation: Kudela E et al. Int J Mol Sci. 2020 Oct 17. doi: 10.3390/ijms21207691.

Key clinical point: Differences in microRNAs (mRNAs), a group of small RNAs that regulate gene expression, can be used to distinguish among breast cancer subtypes.

Major finding: Altered expression of microRNAs distinguished between cancer and healthy samples, and also identified breast cancer subtypes including HER2, Luminal A, Luminal B, and triple negative breast cancer, according to a retrospective study of 740 breast cancer cases included in the review.

Study details: The data come from a review of the latest research on the prognostic and predictive value of microRNAs in patients with luminal A breast cancer.

Disclosures: The study was supported by the Scientific Grant Agency of the Ministry of Education of the Slovak Republic, the Slovak Research and Development Agency, and the Operational Programme Research and Innovation funded by the ERDF.

Citation: Kudela E et al. Int J Mol Sci. 2020 Oct 17. doi: 10.3390/ijms21207691.

Key clinical point: Differences in microRNAs (mRNAs), a group of small RNAs that regulate gene expression, can be used to distinguish among breast cancer subtypes.

Major finding: Altered expression of microRNAs distinguished between cancer and healthy samples, and also identified breast cancer subtypes including HER2, Luminal A, Luminal B, and triple negative breast cancer, according to a retrospective study of 740 breast cancer cases included in the review.

Study details: The data come from a review of the latest research on the prognostic and predictive value of microRNAs in patients with luminal A breast cancer.

Disclosures: The study was supported by the Scientific Grant Agency of the Ministry of Education of the Slovak Republic, the Slovak Research and Development Agency, and the Operational Programme Research and Innovation funded by the ERDF.

Citation: Kudela E et al. Int J Mol Sci. 2020 Oct 17. doi: 10.3390/ijms21207691.

Key clinical point: Over a 12-month period, 15.4% of women with early breast cancer reported losing income. Although stress, anxiety, and depression were not association with household income changes (risk ratios 2.42, 1.12, and 1.41, respectively), the proportion of women reporting high stress was greatest among those who lost income (13.2%, compared to 3.1% among women maintaining an income of $100,000 or higher).

Major finding: Women with a household income below $50,000 had a higher risk of losing household income compared to those with incomes of $50,000 or higher, suggesting that lower income women may be more vulnerable to income loss after diagnosis with breast cancer.

Study details: The data come from a prospective, longitudinal cohort study including 467 women with early breast cancer enrolled in the Young and Strong cohort trial from 2012 to 2013.

Disclosures: The study was supported by an ASCO Improving Cancer Care grant, the National Institutes of Health, an NIH training grants. The researchers had no financial conflicts to disclose.

Citation: Cook EE et al. BMC Public Health. 2020 Oct 6. doi: 10.1186/s12889-020-09562-z.

Key clinical point: Over a 12-month period, 15.4% of women with early breast cancer reported losing income. Although stress, anxiety, and depression were not association with household income changes (risk ratios 2.42, 1.12, and 1.41, respectively), the proportion of women reporting high stress was greatest among those who lost income (13.2%, compared to 3.1% among women maintaining an income of $100,000 or higher).

Major finding: Women with a household income below $50,000 had a higher risk of losing household income compared to those with incomes of $50,000 or higher, suggesting that lower income women may be more vulnerable to income loss after diagnosis with breast cancer.

Study details: The data come from a prospective, longitudinal cohort study including 467 women with early breast cancer enrolled in the Young and Strong cohort trial from 2012 to 2013.

Disclosures: The study was supported by an ASCO Improving Cancer Care grant, the National Institutes of Health, an NIH training grants. The researchers had no financial conflicts to disclose.

Citation: Cook EE et al. BMC Public Health. 2020 Oct 6. doi: 10.1186/s12889-020-09562-z.

Key clinical point: Over a 12-month period, 15.4% of women with early breast cancer reported losing income. Although stress, anxiety, and depression were not association with household income changes (risk ratios 2.42, 1.12, and 1.41, respectively), the proportion of women reporting high stress was greatest among those who lost income (13.2%, compared to 3.1% among women maintaining an income of $100,000 or higher).

Major finding: Women with a household income below $50,000 had a higher risk of losing household income compared to those with incomes of $50,000 or higher, suggesting that lower income women may be more vulnerable to income loss after diagnosis with breast cancer.

Study details: The data come from a prospective, longitudinal cohort study including 467 women with early breast cancer enrolled in the Young and Strong cohort trial from 2012 to 2013.

Disclosures: The study was supported by an ASCO Improving Cancer Care grant, the National Institutes of Health, an NIH training grants. The researchers had no financial conflicts to disclose.

Citation: Cook EE et al. BMC Public Health. 2020 Oct 6. doi: 10.1186/s12889-020-09562-z.