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Immunotherapy could fill unmet need in leptomeningeal metastases
Results from the trial were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.
“Unfortunately, when patients present with leptomeningeal disease, they usually have a poor prognosis. Their median survival is measured at 6-24 weeks,” commented lead study author Jarushka Naidoo, MBBCh, an adjunct assistant professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, and a consultant medical oncologist at Beaumont Hospital in Dublin.
“While there may be some standard approaches for how we treat leptomeningeal disease, there are no universal standard therapies that are efficacious across solid tumor types,” Dr. Naidoo added.
With this in mind, Dr. Naidoo and colleagues tested systemic pembrolizumab in a trial of patients with leptomeningeal metastases from solid tumors.
The trial closed early because of poor accrual, after enrolling 13 patients: 5 with breast carcinoma, 3 with high-grade glioma, 3 with non–small cell lung cancer, 1 with squamous cell carcinoma of the skin, and 1 with head and neck squamous carcinoma. Nine patients (69%) had received at least two prior lines of systemic therapy.
Response, safety, and biomarkers
Overall, five patients (38%) had a central nervous system response, as ascertained from radiologic response on MRI, cytologic response in cerebrospinal fluid (CSF), and/or clinical response in neurologic symptoms, Dr. Naidoo reported.
Two patients had a complete CNS response: a patient with squamous cell carcinoma of the skin, who was still alive at 3 years, and a patient with non–small cell lung cancer, who survived 9 months but succumbed to metastases elsewhere.
For the entire cohort, median CNS progression-free survival was 2.9 months, and median overall survival was 4.9 months.
“This is consistent with published prospective studies of systemic agents for leptomeningeal disease,” Dr. Naidoo pointed out. “Notably, even though numbers are small, we do see the tail-on-the-curve phenomenon in both of these survival curves, which is consistent with immune checkpoint blockade prospective studies.”
The rate of grade 3 or higher treatment-related adverse events was 15.4%, and there were no grade 3 or higher immune-related adverse events.
The number of patients was too small for formal correlational testing, but both patients who achieved a complete response developed immune-related adverse events.
The trial’s biomarker analyses showed that an aneuploidy assay using CSF tumor-derived DNA performed well at detecting leptomeningeal metastases, with sensitivity of 84.6%, compared with just 53.8% for CSF cytopathology (the current preferred method).
A multiplex assay of CSF cytokines identified similar baseline profiles for patients who went on to have responses and showed similar changes in profile (notably a reduction in proinflammatory cytokines) for the two patients who had complete responses.
Given the trial’s 38% CNS response rate, pembrolizumab “needs to be studied in larger populations of patients to confirm this result, but it could be used as a potential treatment option for patients with leptomeningeal disease from solid tumors,” Dr. Naidoo concluded. “Reassuringly, pembrolizumab was well tolerated, and this is extremely important in a patient population that is traditionally quite frail and in which other standard therapies that are used, such as high-dose methotrexate or intrathecal chemotherapy, are associated with far higher rates of toxicity.”
An unmet need
“Leptomeningeal metastasis is a strong unmet need, although its occurrence is fortunately quite rare,” commented Kim Margolin, MD, a clinical professor and medical oncologist at City of Hope National Medical Center in Duarte, Calif., who was not involved in this study.
The trial is noteworthy for showing activity of programmed death–1 (PD-1) blockade given only systemically and not with additional intrathecal therapy (as has been done in a concurrent study at MD Anderson Cancer Center) and for providing insight into various biomarkers, Dr. Margolin said in an interview.
“I cannot take a stand on author conclusions other than to agree it warrants further evaluation in carefully selected patients, and it would be great to compare something like peripheral PD-1 blockade alone versus in combination with intrathecal therapy versus a combination such as CTLA4 blockade plus PD-1 blockade such as our group and others have shown to have increased activity in CNS metastases over PD-1 block alone,” Dr. Margolin said.
“The drugs in this class are already approved, so there is no reason not to try them,” she noted.
However, patients with leptomeningeal metastases of melanoma, for example, are likely to have already received anti-PD-1 immunotherapy.
“So the settings in which off-the-shelf PD-1 blockade would be useful are extremely limited,” she concluded.
The current trial was funded by Merck, the National Institutes of Health, the Lung Cancer Foundation of America, the International Association for the Study of Lung Cancer, and Johns Hopkins University Seed Grants. Dr. Naidoo disclosed relationships with AstraZeneca, Merck, Bristol Myers Squibb, and Roche/Genentech. Dr. Margolin disclosed no relevant conflicts of interest.
SOURCE: Naidoo J et al. SITC 2020, Abstract 788.
Results from the trial were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.
“Unfortunately, when patients present with leptomeningeal disease, they usually have a poor prognosis. Their median survival is measured at 6-24 weeks,” commented lead study author Jarushka Naidoo, MBBCh, an adjunct assistant professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, and a consultant medical oncologist at Beaumont Hospital in Dublin.
“While there may be some standard approaches for how we treat leptomeningeal disease, there are no universal standard therapies that are efficacious across solid tumor types,” Dr. Naidoo added.
With this in mind, Dr. Naidoo and colleagues tested systemic pembrolizumab in a trial of patients with leptomeningeal metastases from solid tumors.
The trial closed early because of poor accrual, after enrolling 13 patients: 5 with breast carcinoma, 3 with high-grade glioma, 3 with non–small cell lung cancer, 1 with squamous cell carcinoma of the skin, and 1 with head and neck squamous carcinoma. Nine patients (69%) had received at least two prior lines of systemic therapy.
Response, safety, and biomarkers
Overall, five patients (38%) had a central nervous system response, as ascertained from radiologic response on MRI, cytologic response in cerebrospinal fluid (CSF), and/or clinical response in neurologic symptoms, Dr. Naidoo reported.
Two patients had a complete CNS response: a patient with squamous cell carcinoma of the skin, who was still alive at 3 years, and a patient with non–small cell lung cancer, who survived 9 months but succumbed to metastases elsewhere.
For the entire cohort, median CNS progression-free survival was 2.9 months, and median overall survival was 4.9 months.
“This is consistent with published prospective studies of systemic agents for leptomeningeal disease,” Dr. Naidoo pointed out. “Notably, even though numbers are small, we do see the tail-on-the-curve phenomenon in both of these survival curves, which is consistent with immune checkpoint blockade prospective studies.”
The rate of grade 3 or higher treatment-related adverse events was 15.4%, and there were no grade 3 or higher immune-related adverse events.
The number of patients was too small for formal correlational testing, but both patients who achieved a complete response developed immune-related adverse events.
The trial’s biomarker analyses showed that an aneuploidy assay using CSF tumor-derived DNA performed well at detecting leptomeningeal metastases, with sensitivity of 84.6%, compared with just 53.8% for CSF cytopathology (the current preferred method).
A multiplex assay of CSF cytokines identified similar baseline profiles for patients who went on to have responses and showed similar changes in profile (notably a reduction in proinflammatory cytokines) for the two patients who had complete responses.
Given the trial’s 38% CNS response rate, pembrolizumab “needs to be studied in larger populations of patients to confirm this result, but it could be used as a potential treatment option for patients with leptomeningeal disease from solid tumors,” Dr. Naidoo concluded. “Reassuringly, pembrolizumab was well tolerated, and this is extremely important in a patient population that is traditionally quite frail and in which other standard therapies that are used, such as high-dose methotrexate or intrathecal chemotherapy, are associated with far higher rates of toxicity.”
An unmet need
“Leptomeningeal metastasis is a strong unmet need, although its occurrence is fortunately quite rare,” commented Kim Margolin, MD, a clinical professor and medical oncologist at City of Hope National Medical Center in Duarte, Calif., who was not involved in this study.
The trial is noteworthy for showing activity of programmed death–1 (PD-1) blockade given only systemically and not with additional intrathecal therapy (as has been done in a concurrent study at MD Anderson Cancer Center) and for providing insight into various biomarkers, Dr. Margolin said in an interview.
“I cannot take a stand on author conclusions other than to agree it warrants further evaluation in carefully selected patients, and it would be great to compare something like peripheral PD-1 blockade alone versus in combination with intrathecal therapy versus a combination such as CTLA4 blockade plus PD-1 blockade such as our group and others have shown to have increased activity in CNS metastases over PD-1 block alone,” Dr. Margolin said.
“The drugs in this class are already approved, so there is no reason not to try them,” she noted.
However, patients with leptomeningeal metastases of melanoma, for example, are likely to have already received anti-PD-1 immunotherapy.
“So the settings in which off-the-shelf PD-1 blockade would be useful are extremely limited,” she concluded.
The current trial was funded by Merck, the National Institutes of Health, the Lung Cancer Foundation of America, the International Association for the Study of Lung Cancer, and Johns Hopkins University Seed Grants. Dr. Naidoo disclosed relationships with AstraZeneca, Merck, Bristol Myers Squibb, and Roche/Genentech. Dr. Margolin disclosed no relevant conflicts of interest.
SOURCE: Naidoo J et al. SITC 2020, Abstract 788.
Results from the trial were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.
“Unfortunately, when patients present with leptomeningeal disease, they usually have a poor prognosis. Their median survival is measured at 6-24 weeks,” commented lead study author Jarushka Naidoo, MBBCh, an adjunct assistant professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, and a consultant medical oncologist at Beaumont Hospital in Dublin.
“While there may be some standard approaches for how we treat leptomeningeal disease, there are no universal standard therapies that are efficacious across solid tumor types,” Dr. Naidoo added.
With this in mind, Dr. Naidoo and colleagues tested systemic pembrolizumab in a trial of patients with leptomeningeal metastases from solid tumors.
The trial closed early because of poor accrual, after enrolling 13 patients: 5 with breast carcinoma, 3 with high-grade glioma, 3 with non–small cell lung cancer, 1 with squamous cell carcinoma of the skin, and 1 with head and neck squamous carcinoma. Nine patients (69%) had received at least two prior lines of systemic therapy.
Response, safety, and biomarkers
Overall, five patients (38%) had a central nervous system response, as ascertained from radiologic response on MRI, cytologic response in cerebrospinal fluid (CSF), and/or clinical response in neurologic symptoms, Dr. Naidoo reported.
Two patients had a complete CNS response: a patient with squamous cell carcinoma of the skin, who was still alive at 3 years, and a patient with non–small cell lung cancer, who survived 9 months but succumbed to metastases elsewhere.
For the entire cohort, median CNS progression-free survival was 2.9 months, and median overall survival was 4.9 months.
“This is consistent with published prospective studies of systemic agents for leptomeningeal disease,” Dr. Naidoo pointed out. “Notably, even though numbers are small, we do see the tail-on-the-curve phenomenon in both of these survival curves, which is consistent with immune checkpoint blockade prospective studies.”
The rate of grade 3 or higher treatment-related adverse events was 15.4%, and there were no grade 3 or higher immune-related adverse events.
The number of patients was too small for formal correlational testing, but both patients who achieved a complete response developed immune-related adverse events.
The trial’s biomarker analyses showed that an aneuploidy assay using CSF tumor-derived DNA performed well at detecting leptomeningeal metastases, with sensitivity of 84.6%, compared with just 53.8% for CSF cytopathology (the current preferred method).
A multiplex assay of CSF cytokines identified similar baseline profiles for patients who went on to have responses and showed similar changes in profile (notably a reduction in proinflammatory cytokines) for the two patients who had complete responses.
Given the trial’s 38% CNS response rate, pembrolizumab “needs to be studied in larger populations of patients to confirm this result, but it could be used as a potential treatment option for patients with leptomeningeal disease from solid tumors,” Dr. Naidoo concluded. “Reassuringly, pembrolizumab was well tolerated, and this is extremely important in a patient population that is traditionally quite frail and in which other standard therapies that are used, such as high-dose methotrexate or intrathecal chemotherapy, are associated with far higher rates of toxicity.”
An unmet need
“Leptomeningeal metastasis is a strong unmet need, although its occurrence is fortunately quite rare,” commented Kim Margolin, MD, a clinical professor and medical oncologist at City of Hope National Medical Center in Duarte, Calif., who was not involved in this study.
The trial is noteworthy for showing activity of programmed death–1 (PD-1) blockade given only systemically and not with additional intrathecal therapy (as has been done in a concurrent study at MD Anderson Cancer Center) and for providing insight into various biomarkers, Dr. Margolin said in an interview.
“I cannot take a stand on author conclusions other than to agree it warrants further evaluation in carefully selected patients, and it would be great to compare something like peripheral PD-1 blockade alone versus in combination with intrathecal therapy versus a combination such as CTLA4 blockade plus PD-1 blockade such as our group and others have shown to have increased activity in CNS metastases over PD-1 block alone,” Dr. Margolin said.
“The drugs in this class are already approved, so there is no reason not to try them,” she noted.
However, patients with leptomeningeal metastases of melanoma, for example, are likely to have already received anti-PD-1 immunotherapy.
“So the settings in which off-the-shelf PD-1 blockade would be useful are extremely limited,” she concluded.
The current trial was funded by Merck, the National Institutes of Health, the Lung Cancer Foundation of America, the International Association for the Study of Lung Cancer, and Johns Hopkins University Seed Grants. Dr. Naidoo disclosed relationships with AstraZeneca, Merck, Bristol Myers Squibb, and Roche/Genentech. Dr. Margolin disclosed no relevant conflicts of interest.
SOURCE: Naidoo J et al. SITC 2020, Abstract 788.
FROM SITC 2020
Breast Cancer Journal Scans: November 2020
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.
MicroRNAs show promising predictive value for early breast cancer
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.
Income loss shows no link to stress levels in young women with breast cancer
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.
Exercise and diet intervention fail to improve fatigue in breast cancer patients on chemotherapy
Key clinical point: An exercise and diet intervention had no significant impact on fatigue in women with breast cancer who were undergoing chemotherapy or radiotherapy.
Major finding: Based on the general cancer-related fatigue score using the MFI-20 questionnaire, general fatigue levels were not significantly different between groups of breast cancer patients randomized to an Adapted Physical Activity Diet (APAD) program and controls (P = 0.274).
Study details: The data come from a randomized, controlled trial of 360 adult women with early breast cancer designed to evaluate the impact of an exercise and nutrition intervention on fatigue during 6 months of chemotherapy and radiotherapy.
Disclosures: The study was supported by the INCa-DGOS and by a Montpellier Cancer SIRIC grant. The researchers had no financial conflicts to disclose.
Citation: Jacot W et al. Nutrients. 2020 Oct 9. doi: 10.3390/nu12103081.
Key clinical point: An exercise and diet intervention had no significant impact on fatigue in women with breast cancer who were undergoing chemotherapy or radiotherapy.
Major finding: Based on the general cancer-related fatigue score using the MFI-20 questionnaire, general fatigue levels were not significantly different between groups of breast cancer patients randomized to an Adapted Physical Activity Diet (APAD) program and controls (P = 0.274).
Study details: The data come from a randomized, controlled trial of 360 adult women with early breast cancer designed to evaluate the impact of an exercise and nutrition intervention on fatigue during 6 months of chemotherapy and radiotherapy.
Disclosures: The study was supported by the INCa-DGOS and by a Montpellier Cancer SIRIC grant. The researchers had no financial conflicts to disclose.
Citation: Jacot W et al. Nutrients. 2020 Oct 9. doi: 10.3390/nu12103081.
Key clinical point: An exercise and diet intervention had no significant impact on fatigue in women with breast cancer who were undergoing chemotherapy or radiotherapy.
Major finding: Based on the general cancer-related fatigue score using the MFI-20 questionnaire, general fatigue levels were not significantly different between groups of breast cancer patients randomized to an Adapted Physical Activity Diet (APAD) program and controls (P = 0.274).
Study details: The data come from a randomized, controlled trial of 360 adult women with early breast cancer designed to evaluate the impact of an exercise and nutrition intervention on fatigue during 6 months of chemotherapy and radiotherapy.
Disclosures: The study was supported by the INCa-DGOS and by a Montpellier Cancer SIRIC grant. The researchers had no financial conflicts to disclose.
Citation: Jacot W et al. Nutrients. 2020 Oct 9. doi: 10.3390/nu12103081.
DNA-based model predicts overall survival in breast cancer
Key clinical point: A prognostic signature including 8 DNA repair-related genes (MDC1, RPA3, MED17, DDB2, SFPQ, XRCC4, CYP19A1, and PARP3) predicted overall survival in breast cancer patients
Major finding: The areas under the curve were for 3-year survival and 5-year survival were 0.717 and 0.772, respectively, in the GSE9893 data set, and 0.691 and 0.718, respectively, in the GSE42568 data set.
Study details: The data come from 1,096 women with breast cancer; gene expression profiles and clinical data were collected from a Chinese health database between October 9, 2019, and February 3, 2020.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Zhang D et al. JAMA Netw Open. 2020 Oct 5. doi:10.1001/jamanetworkopen.2020.14622.
Key clinical point: A prognostic signature including 8 DNA repair-related genes (MDC1, RPA3, MED17, DDB2, SFPQ, XRCC4, CYP19A1, and PARP3) predicted overall survival in breast cancer patients
Major finding: The areas under the curve were for 3-year survival and 5-year survival were 0.717 and 0.772, respectively, in the GSE9893 data set, and 0.691 and 0.718, respectively, in the GSE42568 data set.
Study details: The data come from 1,096 women with breast cancer; gene expression profiles and clinical data were collected from a Chinese health database between October 9, 2019, and February 3, 2020.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Zhang D et al. JAMA Netw Open. 2020 Oct 5. doi:10.1001/jamanetworkopen.2020.14622.
Key clinical point: A prognostic signature including 8 DNA repair-related genes (MDC1, RPA3, MED17, DDB2, SFPQ, XRCC4, CYP19A1, and PARP3) predicted overall survival in breast cancer patients
Major finding: The areas under the curve were for 3-year survival and 5-year survival were 0.717 and 0.772, respectively, in the GSE9893 data set, and 0.691 and 0.718, respectively, in the GSE42568 data set.
Study details: The data come from 1,096 women with breast cancer; gene expression profiles and clinical data were collected from a Chinese health database between October 9, 2019, and February 3, 2020.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Zhang D et al. JAMA Netw Open. 2020 Oct 5. doi:10.1001/jamanetworkopen.2020.14622.
Textured breast implants may raise risk of cancer relapse
Key clinical point: The use of textured implants in reconstructive surgery after breast cancer mastectomy was significantly associated with lower rates of disease-free survival compared to smooth implants, but no difference was noted in local and regional recurrence-free survival based on implant texture.
Major finding: Rates of disease-free survival were significantly lower among breast cancer patients who received textured breast implants compared to those who received smooth implants (hazard ratio 3.054); the association was even stronger among patients with stage II or III tumors (HR 8.874).
Study details: The data come from a cohort study of 650 women representing 687 cases of breast cancer who were treated at a single center in South Korea between January 1, 2011, and December 31, 2016.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Lee K-T et al. JAMA Surg. 2020 Oct 7. doi: 10.1001/jamasurg.2020.4124.
Key clinical point: The use of textured implants in reconstructive surgery after breast cancer mastectomy was significantly associated with lower rates of disease-free survival compared to smooth implants, but no difference was noted in local and regional recurrence-free survival based on implant texture.
Major finding: Rates of disease-free survival were significantly lower among breast cancer patients who received textured breast implants compared to those who received smooth implants (hazard ratio 3.054); the association was even stronger among patients with stage II or III tumors (HR 8.874).
Study details: The data come from a cohort study of 650 women representing 687 cases of breast cancer who were treated at a single center in South Korea between January 1, 2011, and December 31, 2016.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Lee K-T et al. JAMA Surg. 2020 Oct 7. doi: 10.1001/jamasurg.2020.4124.
Key clinical point: The use of textured implants in reconstructive surgery after breast cancer mastectomy was significantly associated with lower rates of disease-free survival compared to smooth implants, but no difference was noted in local and regional recurrence-free survival based on implant texture.
Major finding: Rates of disease-free survival were significantly lower among breast cancer patients who received textured breast implants compared to those who received smooth implants (hazard ratio 3.054); the association was even stronger among patients with stage II or III tumors (HR 8.874).
Study details: The data come from a cohort study of 650 women representing 687 cases of breast cancer who were treated at a single center in South Korea between January 1, 2011, and December 31, 2016.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Lee K-T et al. JAMA Surg. 2020 Oct 7. doi: 10.1001/jamasurg.2020.4124.
Vacuum-assisted biopsy predicts post-treatment residual disease in breast cancer
Key clinical point: Vacuum-assisted biopsy accurately predicted residual disease in breast cancer patients after neoadjuvant chemotherapy.
Major finding: The overall false negative rate using vacuum-assisted biopsy (VAB) was 18.7%; in a subgroup of patients with a complete/partial response and imaging abnormalities of 2 cm or smaller, the false negative rate was 3.2% and the negative predictive value was 97.4% for an overall accuracy of 89.5% with VAB.
Study details: The data come from a diagnostic study of 166 women with breast cancer who received neoadjuvant chemotherapy followed by image-guided biopsy.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Tasoulis MK et al. JAMA Surg. 2020 Oct 7. doi: 10.1001/jamasurg.2020.4103.
Key clinical point: Vacuum-assisted biopsy accurately predicted residual disease in breast cancer patients after neoadjuvant chemotherapy.
Major finding: The overall false negative rate using vacuum-assisted biopsy (VAB) was 18.7%; in a subgroup of patients with a complete/partial response and imaging abnormalities of 2 cm or smaller, the false negative rate was 3.2% and the negative predictive value was 97.4% for an overall accuracy of 89.5% with VAB.
Study details: The data come from a diagnostic study of 166 women with breast cancer who received neoadjuvant chemotherapy followed by image-guided biopsy.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Tasoulis MK et al. JAMA Surg. 2020 Oct 7. doi: 10.1001/jamasurg.2020.4103.
Key clinical point: Vacuum-assisted biopsy accurately predicted residual disease in breast cancer patients after neoadjuvant chemotherapy.
Major finding: The overall false negative rate using vacuum-assisted biopsy (VAB) was 18.7%; in a subgroup of patients with a complete/partial response and imaging abnormalities of 2 cm or smaller, the false negative rate was 3.2% and the negative predictive value was 97.4% for an overall accuracy of 89.5% with VAB.
Study details: The data come from a diagnostic study of 166 women with breast cancer who received neoadjuvant chemotherapy followed by image-guided biopsy.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Tasoulis MK et al. JAMA Surg. 2020 Oct 7. doi: 10.1001/jamasurg.2020.4103.
Immediate breast reconstruction after chemotherapy doesn’t hurt survival
Key clinical point: Outcomes including recurrence, disease-free survival, and overall survival were similar for breast cancer patients who underwent immediate breast reconstruction (IBR) with nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) following neoadjuvant chemotherapy.
Major finding: Breast cancer patients who underwent IBR with NSM/SSM as surgical treatment showed similar rates of overall survival at 5 years compared to those who underwent conventional mastectomy (92.0% vs. 89.3%).
Study details: The data come from a retrospective, case-control study of 1,266 breast cancer patients who underwent neoadjuvant chemotherapy followed by immediate breast reconstruction or conventional mastectomy at a single center between January 1, 2010, and November 30, 2016.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Wu Z-Y et al. JAMA Surg. 2020 Oct 14. doi: 10.1001/jamasurg.2020.4132.
Key clinical point: Outcomes including recurrence, disease-free survival, and overall survival were similar for breast cancer patients who underwent immediate breast reconstruction (IBR) with nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) following neoadjuvant chemotherapy.
Major finding: Breast cancer patients who underwent IBR with NSM/SSM as surgical treatment showed similar rates of overall survival at 5 years compared to those who underwent conventional mastectomy (92.0% vs. 89.3%).
Study details: The data come from a retrospective, case-control study of 1,266 breast cancer patients who underwent neoadjuvant chemotherapy followed by immediate breast reconstruction or conventional mastectomy at a single center between January 1, 2010, and November 30, 2016.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Wu Z-Y et al. JAMA Surg. 2020 Oct 14. doi: 10.1001/jamasurg.2020.4132.
Key clinical point: Outcomes including recurrence, disease-free survival, and overall survival were similar for breast cancer patients who underwent immediate breast reconstruction (IBR) with nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) following neoadjuvant chemotherapy.
Major finding: Breast cancer patients who underwent IBR with NSM/SSM as surgical treatment showed similar rates of overall survival at 5 years compared to those who underwent conventional mastectomy (92.0% vs. 89.3%).
Study details: The data come from a retrospective, case-control study of 1,266 breast cancer patients who underwent neoadjuvant chemotherapy followed by immediate breast reconstruction or conventional mastectomy at a single center between January 1, 2010, and November 30, 2016.
Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.
Citation: Wu Z-Y et al. JAMA Surg. 2020 Oct 14. doi: 10.1001/jamasurg.2020.4132.
Black women show higher rates of three breast cancer subtypes
Key clinical point: Breast cancer subtypes may be associated with race and ethnicity; certain subtypes were significantly more common in Black women and infiltrating duct carcinoma compared to White women, but lobular carcinoma, and tubular adenocarcinoma were less common in Hispanic women compared to nonHispanic White women.
Major finding: The incidence of HR-negative and ERBB2-positive; HR-positive and ERBB2-positive; and triple negative breast cancer was significantly higher among Black women compared to nonHispanic White women, but the incidence of the HR-positive and ERBB2-negative subtype in Black women was lower (incidence rate ratios of 1.12, 1.46, 2.07, and 0.86, respectively).
Study details: The data come from a population-based cohort study of 239,211 women with breast cancer diagnosed between January 1, 2010, and December 31, 2015.
Disclosures: The study was supported by grants to the researchers from several organizations including the Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Special Research Fund for Central Universities, Peking Union Medical College, the Beijing Hope Run Special Fund of Cancer Foundation of China, and the PhD Innovation Fund of Cancer Hospital, Chinese Academy of Medical Sciences. The researchers had no financial conflicts to disclose.
Citation: Kong X et al. JAMA Netw Open. 2020 Oct 19. doi:10.1001/jamanetworkopen.2020.20303.
Key clinical point: Breast cancer subtypes may be associated with race and ethnicity; certain subtypes were significantly more common in Black women and infiltrating duct carcinoma compared to White women, but lobular carcinoma, and tubular adenocarcinoma were less common in Hispanic women compared to nonHispanic White women.
Major finding: The incidence of HR-negative and ERBB2-positive; HR-positive and ERBB2-positive; and triple negative breast cancer was significantly higher among Black women compared to nonHispanic White women, but the incidence of the HR-positive and ERBB2-negative subtype in Black women was lower (incidence rate ratios of 1.12, 1.46, 2.07, and 0.86, respectively).
Study details: The data come from a population-based cohort study of 239,211 women with breast cancer diagnosed between January 1, 2010, and December 31, 2015.
Disclosures: The study was supported by grants to the researchers from several organizations including the Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Special Research Fund for Central Universities, Peking Union Medical College, the Beijing Hope Run Special Fund of Cancer Foundation of China, and the PhD Innovation Fund of Cancer Hospital, Chinese Academy of Medical Sciences. The researchers had no financial conflicts to disclose.
Citation: Kong X et al. JAMA Netw Open. 2020 Oct 19. doi:10.1001/jamanetworkopen.2020.20303.
Key clinical point: Breast cancer subtypes may be associated with race and ethnicity; certain subtypes were significantly more common in Black women and infiltrating duct carcinoma compared to White women, but lobular carcinoma, and tubular adenocarcinoma were less common in Hispanic women compared to nonHispanic White women.
Major finding: The incidence of HR-negative and ERBB2-positive; HR-positive and ERBB2-positive; and triple negative breast cancer was significantly higher among Black women compared to nonHispanic White women, but the incidence of the HR-positive and ERBB2-negative subtype in Black women was lower (incidence rate ratios of 1.12, 1.46, 2.07, and 0.86, respectively).
Study details: The data come from a population-based cohort study of 239,211 women with breast cancer diagnosed between January 1, 2010, and December 31, 2015.
Disclosures: The study was supported by grants to the researchers from several organizations including the Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Special Research Fund for Central Universities, Peking Union Medical College, the Beijing Hope Run Special Fund of Cancer Foundation of China, and the PhD Innovation Fund of Cancer Hospital, Chinese Academy of Medical Sciences. The researchers had no financial conflicts to disclose.
Citation: Kong X et al. JAMA Netw Open. 2020 Oct 19. doi:10.1001/jamanetworkopen.2020.20303.