Key clinical point: Olaparib monotherapy is effective in germline BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer in a real-world setting.

Major finding: The median progression-free survival was 8.11 months, and the clinical response rate was 48.6%. The grade 3 or higher treatment-related adverse event rate was 25.4%. There were no new safety signals.

Study details: An interim analysis of an open-label, single-arm, phase 3b LUCY trial including 252 previously treated patients with HER2-negative metastatic breast cancer with a germline BRCA mutation who received olaparib.

Disclosures: The study was funded by AstraZeneca. Dr. S McCutcheon was an employee and stockholder of AstraZeneca LP. Dr. J Bennett and Dr. G Walker were contractors for AstraZeneca LP. The authors received consulting/speaker fees or research support from various sources.

Source: Gelmon KA et al. Eur J Cancer. 2021 Jun 1. doi: 10.1016/j.ejca.2021.03.029.

Key clinical point: Olaparib monotherapy is effective in germline BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer in a real-world setting.

Major finding: The median progression-free survival was 8.11 months, and the clinical response rate was 48.6%. The grade 3 or higher treatment-related adverse event rate was 25.4%. There were no new safety signals.

Study details: An interim analysis of an open-label, single-arm, phase 3b LUCY trial including 252 previously treated patients with HER2-negative metastatic breast cancer with a germline BRCA mutation who received olaparib.

Disclosures: The study was funded by AstraZeneca. Dr. S McCutcheon was an employee and stockholder of AstraZeneca LP. Dr. J Bennett and Dr. G Walker were contractors for AstraZeneca LP. The authors received consulting/speaker fees or research support from various sources.

Source: Gelmon KA et al. Eur J Cancer. 2021 Jun 1. doi: 10.1016/j.ejca.2021.03.029.

Key clinical point: Olaparib monotherapy is effective in germline BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer in a real-world setting.

Major finding: The median progression-free survival was 8.11 months, and the clinical response rate was 48.6%. The grade 3 or higher treatment-related adverse event rate was 25.4%. There were no new safety signals.

Study details: An interim analysis of an open-label, single-arm, phase 3b LUCY trial including 252 previously treated patients with HER2-negative metastatic breast cancer with a germline BRCA mutation who received olaparib.

Disclosures: The study was funded by AstraZeneca. Dr. S McCutcheon was an employee and stockholder of AstraZeneca LP. Dr. J Bennett and Dr. G Walker were contractors for AstraZeneca LP. The authors received consulting/speaker fees or research support from various sources.

Source: Gelmon KA et al. Eur J Cancer. 2021 Jun 1. doi: 10.1016/j.ejca.2021.03.029.

Key clinical point: The Internet–based-targeted psychological interventions fail to reduce fear of recurrence among early breast cancer survivors.

Major finding: The Fear of Cancer Recurrence Inventory (FCRI) scores significantly decreased at 8 weeks from baseline in all groups (P less than .001). The magnitude of reduction in FCRI scores was similar in cognitive-behavioral interventions and attention controls.

Study details: The randomized controlled FoRtitude study of breast cancer survivors who completed primary treatment. The survivors were randomly assigned to 4 Internet-based interventions or controls. The 4 interventions given for 4 weeks consisted of 3 cognitive behavioral interventions (relaxation, cognitive restructuring, and worry practice vs. attention controls) and telecoaching (motivational interviewing to improve adherence vs. no telecoaching).

Disclosures: This work was supported by the National Cancer Institute at the National Institutes of Health and the ECOG-ACRIN Medical Research Foundation. The authors did not disclose any conflict of interest.

Source: Wagner LI. J Natl Cancer Inst. 2021 May 31. doi: 10.1093/jnci/djab100.

Key clinical point: The Internet–based-targeted psychological interventions fail to reduce fear of recurrence among early breast cancer survivors.

Major finding: The Fear of Cancer Recurrence Inventory (FCRI) scores significantly decreased at 8 weeks from baseline in all groups (P less than .001). The magnitude of reduction in FCRI scores was similar in cognitive-behavioral interventions and attention controls.

Study details: The randomized controlled FoRtitude study of breast cancer survivors who completed primary treatment. The survivors were randomly assigned to 4 Internet-based interventions or controls. The 4 interventions given for 4 weeks consisted of 3 cognitive behavioral interventions (relaxation, cognitive restructuring, and worry practice vs. attention controls) and telecoaching (motivational interviewing to improve adherence vs. no telecoaching).

Disclosures: This work was supported by the National Cancer Institute at the National Institutes of Health and the ECOG-ACRIN Medical Research Foundation. The authors did not disclose any conflict of interest.

Source: Wagner LI. J Natl Cancer Inst. 2021 May 31. doi: 10.1093/jnci/djab100.

Key clinical point: The Internet–based-targeted psychological interventions fail to reduce fear of recurrence among early breast cancer survivors.

Major finding: The Fear of Cancer Recurrence Inventory (FCRI) scores significantly decreased at 8 weeks from baseline in all groups (P less than .001). The magnitude of reduction in FCRI scores was similar in cognitive-behavioral interventions and attention controls.

Study details: The randomized controlled FoRtitude study of breast cancer survivors who completed primary treatment. The survivors were randomly assigned to 4 Internet-based interventions or controls. The 4 interventions given for 4 weeks consisted of 3 cognitive behavioral interventions (relaxation, cognitive restructuring, and worry practice vs. attention controls) and telecoaching (motivational interviewing to improve adherence vs. no telecoaching).

Disclosures: This work was supported by the National Cancer Institute at the National Institutes of Health and the ECOG-ACRIN Medical Research Foundation. The authors did not disclose any conflict of interest.

Source: Wagner LI. J Natl Cancer Inst. 2021 May 31. doi: 10.1093/jnci/djab100.

Key clinical point: The survival among patients with metastatic breast cancer has improved over past 3 decades.

Major finding: During 1988-2015, 1-year overall survival (OS) rate increased from 62.3% to 72.4% and 1-year cancer-specific survival (CSS) rate increased from 64.7% to 74.1%. Similarly, 5-year OS rate increased from 19.4% to 24.3% and 5-year CSS rate increased from 23.4% to 28.0% during 1998-2011.

Study details: A retrospective cohort study of 47,034 patients with de novo metastatic breast cancer in the Surveillance, Epidemiology, and End Results database from 1988 to 2016.

Disclosures: This study is in part supported by Duke Cancer Institute. Dr. OM Fayanju is supported by the National Institutes of Health. Some of the authors received research funding and consulting/advisory fees from various sources. Dr. JK Plichta and Dr. ES Hwang have served on various Cancer Committees. The other authors reported no competing interests.

Source: Taskindoust M. Ann Surg Oncol. 2021 May 28. doi: 10.1245/s10434-021-10227-3.

Key clinical point: The survival among patients with metastatic breast cancer has improved over past 3 decades.

Major finding: During 1988-2015, 1-year overall survival (OS) rate increased from 62.3% to 72.4% and 1-year cancer-specific survival (CSS) rate increased from 64.7% to 74.1%. Similarly, 5-year OS rate increased from 19.4% to 24.3% and 5-year CSS rate increased from 23.4% to 28.0% during 1998-2011.

Study details: A retrospective cohort study of 47,034 patients with de novo metastatic breast cancer in the Surveillance, Epidemiology, and End Results database from 1988 to 2016.

Disclosures: This study is in part supported by Duke Cancer Institute. Dr. OM Fayanju is supported by the National Institutes of Health. Some of the authors received research funding and consulting/advisory fees from various sources. Dr. JK Plichta and Dr. ES Hwang have served on various Cancer Committees. The other authors reported no competing interests.

Source: Taskindoust M. Ann Surg Oncol. 2021 May 28. doi: 10.1245/s10434-021-10227-3.

Key clinical point: The survival among patients with metastatic breast cancer has improved over past 3 decades.

Major finding: During 1988-2015, 1-year overall survival (OS) rate increased from 62.3% to 72.4% and 1-year cancer-specific survival (CSS) rate increased from 64.7% to 74.1%. Similarly, 5-year OS rate increased from 19.4% to 24.3% and 5-year CSS rate increased from 23.4% to 28.0% during 1998-2011.

Study details: A retrospective cohort study of 47,034 patients with de novo metastatic breast cancer in the Surveillance, Epidemiology, and End Results database from 1988 to 2016.

Disclosures: This study is in part supported by Duke Cancer Institute. Dr. OM Fayanju is supported by the National Institutes of Health. Some of the authors received research funding and consulting/advisory fees from various sources. Dr. JK Plichta and Dr. ES Hwang have served on various Cancer Committees. The other authors reported no competing interests.

Source: Taskindoust M. Ann Surg Oncol. 2021 May 28. doi: 10.1245/s10434-021-10227-3.

Key clinical point: In patients with triple-negative breast cancer (TNBC), the risk for locoregional recurrence and distant metastasis is lower when treated with breast-conserving surgery (BCS) vs. mastectomy.

Major finding: BCS vs. mastectomy was associated with lower risk for locoregional recurrence (unadjusted pooled odds ratio, 0.64; P = .002). The risk for distant metastasis was also significantly lower with BCS vs. mastectomy (unadjusted pooled odds ratio, 0.70; P = .02).

Study details: A meta-analysis of 14 studies including 19,819 patients with TNBC who underwent either BCS or mastectomy.

Disclosures: This meta-analysis was supported by investigator grants from the National Health and Medical Research Council and the National Breast Cancer Foundation. The authors declared no conflicts of interest.

Source: Fancellu A. Br J Surg. 2021 May 31. doi: 10.1093/bjs/znab145.

Key clinical point: In patients with triple-negative breast cancer (TNBC), the risk for locoregional recurrence and distant metastasis is lower when treated with breast-conserving surgery (BCS) vs. mastectomy.

Major finding: BCS vs. mastectomy was associated with lower risk for locoregional recurrence (unadjusted pooled odds ratio, 0.64; P = .002). The risk for distant metastasis was also significantly lower with BCS vs. mastectomy (unadjusted pooled odds ratio, 0.70; P = .02).

Study details: A meta-analysis of 14 studies including 19,819 patients with TNBC who underwent either BCS or mastectomy.

Disclosures: This meta-analysis was supported by investigator grants from the National Health and Medical Research Council and the National Breast Cancer Foundation. The authors declared no conflicts of interest.

Source: Fancellu A. Br J Surg. 2021 May 31. doi: 10.1093/bjs/znab145.

Key clinical point: In patients with triple-negative breast cancer (TNBC), the risk for locoregional recurrence and distant metastasis is lower when treated with breast-conserving surgery (BCS) vs. mastectomy.

Major finding: BCS vs. mastectomy was associated with lower risk for locoregional recurrence (unadjusted pooled odds ratio, 0.64; P = .002). The risk for distant metastasis was also significantly lower with BCS vs. mastectomy (unadjusted pooled odds ratio, 0.70; P = .02).

Study details: A meta-analysis of 14 studies including 19,819 patients with TNBC who underwent either BCS or mastectomy.

Disclosures: This meta-analysis was supported by investigator grants from the National Health and Medical Research Council and the National Breast Cancer Foundation. The authors declared no conflicts of interest.

Source: Fancellu A. Br J Surg. 2021 May 31. doi: 10.1093/bjs/znab145.

Key clinical point: Patients with hormone receptor (HR)-positive breast cancer derive survival benefit from treatment with predominantly aromatase inhibitors after chemotherapy.

Major finding: The recurrence-free survival significantly improved in patients who received aromatase inhibitor for greater than 75% of their endocrine treatment duration (adjusted hazard ratio [aHR], 0.63; 95% confidence interval [CI], 0.46-0.86) and overall survival (aHR, 0.50; 95% CI, 0.34-0.74) vs. those who received aromatase inhibitors for less than 25% of their endocrine treatment duration.

Study details: A population-based cohort study of patients with stage I-III, HR-positive invasive breast cancer diagnosed between 2004 and 2007 and received adjuvant chemotherapy and endocrine treatment.

Disclosures: This work was funded by the Netherlands Organization for Health Research and Development, A Sisters Hope, and De Vrienden van UMC Utrecht. Some authors reported research support, grants, advisory fees, and nonfinancial support from various sources outside this work.

Source: Dackus GM et al. J Natl Cancer Inst. 2021 Jun 8. doi: 10.1093/jnci/djab091.

Key clinical point: Patients with hormone receptor (HR)-positive breast cancer derive survival benefit from treatment with predominantly aromatase inhibitors after chemotherapy.

Major finding: The recurrence-free survival significantly improved in patients who received aromatase inhibitor for greater than 75% of their endocrine treatment duration (adjusted hazard ratio [aHR], 0.63; 95% confidence interval [CI], 0.46-0.86) and overall survival (aHR, 0.50; 95% CI, 0.34-0.74) vs. those who received aromatase inhibitors for less than 25% of their endocrine treatment duration.

Study details: A population-based cohort study of patients with stage I-III, HR-positive invasive breast cancer diagnosed between 2004 and 2007 and received adjuvant chemotherapy and endocrine treatment.

Disclosures: This work was funded by the Netherlands Organization for Health Research and Development, A Sisters Hope, and De Vrienden van UMC Utrecht. Some authors reported research support, grants, advisory fees, and nonfinancial support from various sources outside this work.

Source: Dackus GM et al. J Natl Cancer Inst. 2021 Jun 8. doi: 10.1093/jnci/djab091.

Key clinical point: Patients with hormone receptor (HR)-positive breast cancer derive survival benefit from treatment with predominantly aromatase inhibitors after chemotherapy.

Major finding: The recurrence-free survival significantly improved in patients who received aromatase inhibitor for greater than 75% of their endocrine treatment duration (adjusted hazard ratio [aHR], 0.63; 95% confidence interval [CI], 0.46-0.86) and overall survival (aHR, 0.50; 95% CI, 0.34-0.74) vs. those who received aromatase inhibitors for less than 25% of their endocrine treatment duration.

Study details: A population-based cohort study of patients with stage I-III, HR-positive invasive breast cancer diagnosed between 2004 and 2007 and received adjuvant chemotherapy and endocrine treatment.

Disclosures: This work was funded by the Netherlands Organization for Health Research and Development, A Sisters Hope, and De Vrienden van UMC Utrecht. Some authors reported research support, grants, advisory fees, and nonfinancial support from various sources outside this work.

Source: Dackus GM et al. J Natl Cancer Inst. 2021 Jun 8. doi: 10.1093/jnci/djab091.

Key clinical point: In patients with hormone receptor (HR)-positive, human epidermal growth receptor (HER)-negative advanced breast cancer, the addition of ribociclib to fulvestrant extends median overall survival by 12 months.

Major finding: The median overall survival was 53.7 months with ribociclib and 41.5 months with placebo (hazard ratio, 0.73; 95% confidence interval, 0.59-0.90 months) at a median follow-up of 56.3 months. Neutropenia was the most common grade 3-4 adverse event.

Study details: A phase 3, randomized, double-blind, placebo-controlled MONALEESA-3 trial including 726 chemotherapy-naïve patients (men and postmenopausal women) with HR-positive, HER2-negative advanced breast cancer randomly assigned 2:1 to receive fulvestrant with either ribociclib or placebo.

Disclosures: The study was funded by the Novartis Pharmaceuticals Corporation. The authors reported advisory/consulting fees, stock ownership, research funding, grants, personal fees, honoraria, travel expenses, and nonfinancial support from various sources outside this work.

Source: Slamon DJ et al. Ann Oncol. 2021 Jun 5. doi: 10.1016/j.annonc.2021.05.353.

Key clinical point: In patients with hormone receptor (HR)-positive, human epidermal growth receptor (HER)-negative advanced breast cancer, the addition of ribociclib to fulvestrant extends median overall survival by 12 months.

Major finding: The median overall survival was 53.7 months with ribociclib and 41.5 months with placebo (hazard ratio, 0.73; 95% confidence interval, 0.59-0.90 months) at a median follow-up of 56.3 months. Neutropenia was the most common grade 3-4 adverse event.

Study details: A phase 3, randomized, double-blind, placebo-controlled MONALEESA-3 trial including 726 chemotherapy-naïve patients (men and postmenopausal women) with HR-positive, HER2-negative advanced breast cancer randomly assigned 2:1 to receive fulvestrant with either ribociclib or placebo.

Disclosures: The study was funded by the Novartis Pharmaceuticals Corporation. The authors reported advisory/consulting fees, stock ownership, research funding, grants, personal fees, honoraria, travel expenses, and nonfinancial support from various sources outside this work.

Source: Slamon DJ et al. Ann Oncol. 2021 Jun 5. doi: 10.1016/j.annonc.2021.05.353.

Key clinical point: In patients with hormone receptor (HR)-positive, human epidermal growth receptor (HER)-negative advanced breast cancer, the addition of ribociclib to fulvestrant extends median overall survival by 12 months.

Major finding: The median overall survival was 53.7 months with ribociclib and 41.5 months with placebo (hazard ratio, 0.73; 95% confidence interval, 0.59-0.90 months) at a median follow-up of 56.3 months. Neutropenia was the most common grade 3-4 adverse event.

Study details: A phase 3, randomized, double-blind, placebo-controlled MONALEESA-3 trial including 726 chemotherapy-naïve patients (men and postmenopausal women) with HR-positive, HER2-negative advanced breast cancer randomly assigned 2:1 to receive fulvestrant with either ribociclib or placebo.

Disclosures: The study was funded by the Novartis Pharmaceuticals Corporation. The authors reported advisory/consulting fees, stock ownership, research funding, grants, personal fees, honoraria, travel expenses, and nonfinancial support from various sources outside this work.

Source: Slamon DJ et al. Ann Oncol. 2021 Jun 5. doi: 10.1016/j.annonc.2021.05.353.

Key clinical point: Platinum agents do not improve outcomes in patients with basal subtype triple-negative breast cancer (TNBC) and residual invasive disease post-neoadjuvant chemotherapy (NAC) and are associated with higher toxicity rate vs. capecitabine.

Major finding: The invasive disease-free survival was not significantly different between platinum and capecitabine groups (hazard ratio, 1.06; 95% confidence interval, 0.62-1.81) after a median follow-up of 20 months. Grade 3 and 4 toxicities were more frequent in the platinum vs. capecitabine group (26% vs. 15%).

Study details: A phase 3, randomized controlled EA1131 trial involving 415 patients with stage II-III TNBC post-NAC, randomly assigned to receive platinum-based chemotherapy or capecitabine.

Disclosures: This study was supported by the National Cancer Institute of the National Institutes of Health. The authors received consulting/advisory fees, research funding, honoraria, travel/accommodation/expenses, and reported stock and other ownership interests in various companies. Some authors also reported patents, royalties, and other intellectual property.

Source: Mayer IA et al. J Clin Oncol. 2021 Jun 6. doi: 10.1200/JCO.21.00976.

Key clinical point: Platinum agents do not improve outcomes in patients with basal subtype triple-negative breast cancer (TNBC) and residual invasive disease post-neoadjuvant chemotherapy (NAC) and are associated with higher toxicity rate vs. capecitabine.

Major finding: The invasive disease-free survival was not significantly different between platinum and capecitabine groups (hazard ratio, 1.06; 95% confidence interval, 0.62-1.81) after a median follow-up of 20 months. Grade 3 and 4 toxicities were more frequent in the platinum vs. capecitabine group (26% vs. 15%).

Study details: A phase 3, randomized controlled EA1131 trial involving 415 patients with stage II-III TNBC post-NAC, randomly assigned to receive platinum-based chemotherapy or capecitabine.

Disclosures: This study was supported by the National Cancer Institute of the National Institutes of Health. The authors received consulting/advisory fees, research funding, honoraria, travel/accommodation/expenses, and reported stock and other ownership interests in various companies. Some authors also reported patents, royalties, and other intellectual property.

Source: Mayer IA et al. J Clin Oncol. 2021 Jun 6. doi: 10.1200/JCO.21.00976.

Key clinical point: Platinum agents do not improve outcomes in patients with basal subtype triple-negative breast cancer (TNBC) and residual invasive disease post-neoadjuvant chemotherapy (NAC) and are associated with higher toxicity rate vs. capecitabine.

Major finding: The invasive disease-free survival was not significantly different between platinum and capecitabine groups (hazard ratio, 1.06; 95% confidence interval, 0.62-1.81) after a median follow-up of 20 months. Grade 3 and 4 toxicities were more frequent in the platinum vs. capecitabine group (26% vs. 15%).

Study details: A phase 3, randomized controlled EA1131 trial involving 415 patients with stage II-III TNBC post-NAC, randomly assigned to receive platinum-based chemotherapy or capecitabine.

Disclosures: This study was supported by the National Cancer Institute of the National Institutes of Health. The authors received consulting/advisory fees, research funding, honoraria, travel/accommodation/expenses, and reported stock and other ownership interests in various companies. Some authors also reported patents, royalties, and other intellectual property.

Source: Mayer IA et al. J Clin Oncol. 2021 Jun 6. doi: 10.1200/JCO.21.00976.

Key clinical point: Adjuvant olaparib prolongs invasive disease-free survival and distant disease-free survival in patients with high-risk BRCA1/2-mutated human epidermal growth factor 2 (HER2)-negative early breast cancer who received local treatment and adjuvant/neoadjuvant chemotherapy.

Major finding: Adjuvant olaparib significantly improved invasive disease-free survival (hazard ratio, 0.58; P less than .001) and distant disease-free survival (hazard ratio, 0.57; P less than .001). The serious adverse event rate was 8.7% in the olaparib group and 8.4% in the placebo group.

Study details: A phase 3 double-blind, randomized OlympiA trial evaluated 1,836 patients with high-risk BRCA1/2-mutated HER2-negative early breast cancer who received local treatment and adjuvant/neoadjuvant chemotherapy. Patients were randomly assigned to olaparib or placebo.

Disclosures: The study received funding from the National Cancer Institute and AstraZeneca. The authors reported receiving grants, honoraria, advisory/speaker/consulting fees, financial/nonfinancial support, and travel expense from various sources and/or owning stocks in pharmaceutical companies. Dr. SJ Hollingsworth, Dr. A Fielding, and Dr. N Baker were employees at AstraZeneca.

Source: Tutt ANJ et al. New Eng J Med. 2021 Jun 3. doi: 10.1056/NEJMoa2105215.

Key clinical point: Adjuvant olaparib prolongs invasive disease-free survival and distant disease-free survival in patients with high-risk BRCA1/2-mutated human epidermal growth factor 2 (HER2)-negative early breast cancer who received local treatment and adjuvant/neoadjuvant chemotherapy.

Major finding: Adjuvant olaparib significantly improved invasive disease-free survival (hazard ratio, 0.58; P less than .001) and distant disease-free survival (hazard ratio, 0.57; P less than .001). The serious adverse event rate was 8.7% in the olaparib group and 8.4% in the placebo group.

Study details: A phase 3 double-blind, randomized OlympiA trial evaluated 1,836 patients with high-risk BRCA1/2-mutated HER2-negative early breast cancer who received local treatment and adjuvant/neoadjuvant chemotherapy. Patients were randomly assigned to olaparib or placebo.

Disclosures: The study received funding from the National Cancer Institute and AstraZeneca. The authors reported receiving grants, honoraria, advisory/speaker/consulting fees, financial/nonfinancial support, and travel expense from various sources and/or owning stocks in pharmaceutical companies. Dr. SJ Hollingsworth, Dr. A Fielding, and Dr. N Baker were employees at AstraZeneca.

Source: Tutt ANJ et al. New Eng J Med. 2021 Jun 3. doi: 10.1056/NEJMoa2105215.

Key clinical point: Adjuvant olaparib prolongs invasive disease-free survival and distant disease-free survival in patients with high-risk BRCA1/2-mutated human epidermal growth factor 2 (HER2)-negative early breast cancer who received local treatment and adjuvant/neoadjuvant chemotherapy.

Major finding: Adjuvant olaparib significantly improved invasive disease-free survival (hazard ratio, 0.58; P less than .001) and distant disease-free survival (hazard ratio, 0.57; P less than .001). The serious adverse event rate was 8.7% in the olaparib group and 8.4% in the placebo group.

Study details: A phase 3 double-blind, randomized OlympiA trial evaluated 1,836 patients with high-risk BRCA1/2-mutated HER2-negative early breast cancer who received local treatment and adjuvant/neoadjuvant chemotherapy. Patients were randomly assigned to olaparib or placebo.

Disclosures: The study received funding from the National Cancer Institute and AstraZeneca. The authors reported receiving grants, honoraria, advisory/speaker/consulting fees, financial/nonfinancial support, and travel expense from various sources and/or owning stocks in pharmaceutical companies. Dr. SJ Hollingsworth, Dr. A Fielding, and Dr. N Baker were employees at AstraZeneca.

Source: Tutt ANJ et al. New Eng J Med. 2021 Jun 3. doi: 10.1056/NEJMoa2105215.

The role of adjuvant olaparib was investigated in the phase 3 OlympiA trial, which included 1,836 patients with high-risk HER2-negative gBRCAm early breast cancer who received local treatment and adjuvant or neoadjuvant chemotherapy. One year of adjuvant olaparib was associated with a significant improvement in invasive disease-free survival (hazard ratio [HR] 0.58, P < .001) and distant disease-free survival (HR 0.57, P < .001). The 3-year invasive disease-free survival (iDFS) was 85.9% in the olaparib group and 77.1% in the placebo group (absolute benefit of 8.8%), and 3-year distant disease-free survival (dDFS) was 87.5% and 80.4%, respectively (difference of 7.1%). These results are considered practice changing and lead to questions regarding the expansion of germline testing in early stage breast cancer. Furthermore, PARP inhibitors have shown exciting results in the neoadjuvant setting. Among 61 patients with gBRCAm HER2-negative early breast cancer, neoadjuvant talazoparib produced a pathologic complete response (pCR) in 49.2%, and there may be a subgroup of patients for whom this approach is relevant.

The presence of residual disease after neoadjuvant chemotherapy has prognostic implications and can help tailor adjuvant treatment recommendations. The CREATE-X trial has established the role of adjuvant capecitabine for patients with triple-negative breast cancer with residual disease after pre-operative chemotherapy. The phase 3 EA1131 trial randomized 415 patients with stage II-III triple-negative breast cancer and residual disease post-neoadjuvant chemotherapy to platinum agent or capecitabine. There was no significant difference in 3-year iDFS (42% for platinum vs 49% for capecitabine; HR 1.06, 95% CI 0.62-1.81), and higher hematologic toxicity and dose reductions in the platinum arm. These data support the continued use of capecitabine in this population, and the high event rate highlights the need for more effective therapies in this setting.

The majority of patients with HR+/HER2- MBC will receive a CDK 4/6 inhibitor at some point during their treatment course. In an updated analysis of the phase 3 MONALEESA-3 trial which included postmenopausal patients with HR+HER2- MBC, with median follow-up of 56.3 months, ribociclib plus fulvestrant continued to show an overall survival (OS) benefit of greater than 1 year compared with fulvestrant alone (median OS 53.7 months vs 41.5 months in the ribociclib vs placebo arm, respectively; HR 0.726, 95% CI 0.59-0.90). Additionally, extended follow-up of the PALOMA-3 trial demonstrated OS benefit with palbociclib plus fulvestrant compared to fulvestrant alone in patients with HR+/HER2- MBC; at median follow-up of 73.3 months, median OS was 34.8 months in the palbociclib arm vs 28.0 months in the placebo arm (HR 0.81, P = .0221). Sequencing of other targeted therapies (such as PI3K inhibitors), predictors of CDK 4/6 inhibitor response in different intrinsic subtypes, and the role of CDK 4/6 inhibitor use beyond progression are areas where further research is warranted.

References:

Robson M, Im SA, Senkus E, et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017;377(6):523-533.

Litton JK, Beck JT, Jones JM, et al. Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study. J Clin Oncol 39, 2021 (suppl 15; abstr 505).

Symmans WF, Wei C, Gould R, et al. Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype. J Clin Oncol. 2017;35:1049-1060.

Masuda N, Lee SJ, Ohtani S, et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017;376:2147-2159.

Cristofanilli M, Rugo H, Im SA, et al. Overall survival (OS) with palbociclib (PAL) + fulvestrant (FUL) in women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): Updated analyses from PALOMA-3. J Clin Oncol. 2021; 39:15_suppl, 1000-1000.

The role of adjuvant olaparib was investigated in the phase 3 OlympiA trial, which included 1,836 patients with high-risk HER2-negative gBRCAm early breast cancer who received local treatment and adjuvant or neoadjuvant chemotherapy. One year of adjuvant olaparib was associated with a significant improvement in invasive disease-free survival (hazard ratio [HR] 0.58, P < .001) and distant disease-free survival (HR 0.57, P < .001). The 3-year invasive disease-free survival (iDFS) was 85.9% in the olaparib group and 77.1% in the placebo group (absolute benefit of 8.8%), and 3-year distant disease-free survival (dDFS) was 87.5% and 80.4%, respectively (difference of 7.1%). These results are considered practice changing and lead to questions regarding the expansion of germline testing in early stage breast cancer. Furthermore, PARP inhibitors have shown exciting results in the neoadjuvant setting. Among 61 patients with gBRCAm HER2-negative early breast cancer, neoadjuvant talazoparib produced a pathologic complete response (pCR) in 49.2%, and there may be a subgroup of patients for whom this approach is relevant.

The presence of residual disease after neoadjuvant chemotherapy has prognostic implications and can help tailor adjuvant treatment recommendations. The CREATE-X trial has established the role of adjuvant capecitabine for patients with triple-negative breast cancer with residual disease after pre-operative chemotherapy. The phase 3 EA1131 trial randomized 415 patients with stage II-III triple-negative breast cancer and residual disease post-neoadjuvant chemotherapy to platinum agent or capecitabine. There was no significant difference in 3-year iDFS (42% for platinum vs 49% for capecitabine; HR 1.06, 95% CI 0.62-1.81), and higher hematologic toxicity and dose reductions in the platinum arm. These data support the continued use of capecitabine in this population, and the high event rate highlights the need for more effective therapies in this setting.

The majority of patients with HR+/HER2- MBC will receive a CDK 4/6 inhibitor at some point during their treatment course. In an updated analysis of the phase 3 MONALEESA-3 trial which included postmenopausal patients with HR+HER2- MBC, with median follow-up of 56.3 months, ribociclib plus fulvestrant continued to show an overall survival (OS) benefit of greater than 1 year compared with fulvestrant alone (median OS 53.7 months vs 41.5 months in the ribociclib vs placebo arm, respectively; HR 0.726, 95% CI 0.59-0.90). Additionally, extended follow-up of the PALOMA-3 trial demonstrated OS benefit with palbociclib plus fulvestrant compared to fulvestrant alone in patients with HR+/HER2- MBC; at median follow-up of 73.3 months, median OS was 34.8 months in the palbociclib arm vs 28.0 months in the placebo arm (HR 0.81, P = .0221). Sequencing of other targeted therapies (such as PI3K inhibitors), predictors of CDK 4/6 inhibitor response in different intrinsic subtypes, and the role of CDK 4/6 inhibitor use beyond progression are areas where further research is warranted.

References:

Robson M, Im SA, Senkus E, et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017;377(6):523-533.

Litton JK, Beck JT, Jones JM, et al. Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study. J Clin Oncol 39, 2021 (suppl 15; abstr 505).

Symmans WF, Wei C, Gould R, et al. Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype. J Clin Oncol. 2017;35:1049-1060.

Masuda N, Lee SJ, Ohtani S, et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017;376:2147-2159.

Cristofanilli M, Rugo H, Im SA, et al. Overall survival (OS) with palbociclib (PAL) + fulvestrant (FUL) in women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): Updated analyses from PALOMA-3. J Clin Oncol. 2021; 39:15_suppl, 1000-1000.

The role of adjuvant olaparib was investigated in the phase 3 OlympiA trial, which included 1,836 patients with high-risk HER2-negative gBRCAm early breast cancer who received local treatment and adjuvant or neoadjuvant chemotherapy. One year of adjuvant olaparib was associated with a significant improvement in invasive disease-free survival (hazard ratio [HR] 0.58, P < .001) and distant disease-free survival (HR 0.57, P < .001). The 3-year invasive disease-free survival (iDFS) was 85.9% in the olaparib group and 77.1% in the placebo group (absolute benefit of 8.8%), and 3-year distant disease-free survival (dDFS) was 87.5% and 80.4%, respectively (difference of 7.1%). These results are considered practice changing and lead to questions regarding the expansion of germline testing in early stage breast cancer. Furthermore, PARP inhibitors have shown exciting results in the neoadjuvant setting. Among 61 patients with gBRCAm HER2-negative early breast cancer, neoadjuvant talazoparib produced a pathologic complete response (pCR) in 49.2%, and there may be a subgroup of patients for whom this approach is relevant.

The presence of residual disease after neoadjuvant chemotherapy has prognostic implications and can help tailor adjuvant treatment recommendations. The CREATE-X trial has established the role of adjuvant capecitabine for patients with triple-negative breast cancer with residual disease after pre-operative chemotherapy. The phase 3 EA1131 trial randomized 415 patients with stage II-III triple-negative breast cancer and residual disease post-neoadjuvant chemotherapy to platinum agent or capecitabine. There was no significant difference in 3-year iDFS (42% for platinum vs 49% for capecitabine; HR 1.06, 95% CI 0.62-1.81), and higher hematologic toxicity and dose reductions in the platinum arm. These data support the continued use of capecitabine in this population, and the high event rate highlights the need for more effective therapies in this setting.

The majority of patients with HR+/HER2- MBC will receive a CDK 4/6 inhibitor at some point during their treatment course. In an updated analysis of the phase 3 MONALEESA-3 trial which included postmenopausal patients with HR+HER2- MBC, with median follow-up of 56.3 months, ribociclib plus fulvestrant continued to show an overall survival (OS) benefit of greater than 1 year compared with fulvestrant alone (median OS 53.7 months vs 41.5 months in the ribociclib vs placebo arm, respectively; HR 0.726, 95% CI 0.59-0.90). Additionally, extended follow-up of the PALOMA-3 trial demonstrated OS benefit with palbociclib plus fulvestrant compared to fulvestrant alone in patients with HR+/HER2- MBC; at median follow-up of 73.3 months, median OS was 34.8 months in the palbociclib arm vs 28.0 months in the placebo arm (HR 0.81, P = .0221). Sequencing of other targeted therapies (such as PI3K inhibitors), predictors of CDK 4/6 inhibitor response in different intrinsic subtypes, and the role of CDK 4/6 inhibitor use beyond progression are areas where further research is warranted.

References:

Robson M, Im SA, Senkus E, et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017;377(6):523-533.

Litton JK, Beck JT, Jones JM, et al. Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study. J Clin Oncol 39, 2021 (suppl 15; abstr 505).

Symmans WF, Wei C, Gould R, et al. Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype. J Clin Oncol. 2017;35:1049-1060.

Masuda N, Lee SJ, Ohtani S, et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017;376:2147-2159.

Cristofanilli M, Rugo H, Im SA, et al. Overall survival (OS) with palbociclib (PAL) + fulvestrant (FUL) in women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): Updated analyses from PALOMA-3. J Clin Oncol. 2021; 39:15_suppl, 1000-1000.

THE CASE

A 5-year-old previously healthy white boy presented to clinic with bilateral calf pain and refusal to bear weight since awakening that morning. Associated symptoms included a 3-day history of generalized fatigue, subjective fevers, cough, congestion, and rhinitis. The night prior to presentation, he showed no symptoms of gait abnormalities, muscle pain, or weakness. There was no history of similar symptoms, trauma, overexertion, foreign travel, or family history of musculoskeletal disease. He was fully immunized, except for the annual influenza vaccine. He was not taking any medications. This case occurred before the onset of the COVID-19 pandemic.

Objective findings included fever of 101 °F, refusal to bear weight, and symmetrical bilateral tenderness to palpation of the gastrocnemius-soleus complex. Pain was elicited with passive dorsiflexion. There was no erythema, edema, or sensory deficits, and the distal leg compartments were soft. There was normal range of motion of the hips, knees, and ankles. Dorsalis pedis pulses were 2+, and patella reflexes were 2/4 bilaterally.

Lab results included a white blood cell count of 2500/μL (normal range, 4500 to 11,000/μL);absolute neutrophil count, 900/μL (1500 to 8000/μL); platelet count, 131,000/μL (150,000 to 450,000/μL); creatine kinase level, 869 IU/L (22 to 198 U/L); and aspartate aminotransferase level, 116 U/L (8 to 33 U/L). A rapid influenza swab was positive for influenza B. Plain films of the bilateral hips and lower extremities were unremarkable. C-reactive protein (CRP) level, urinalysis, and renal function tests were within normal limits. Creatine kinase (CK) level peaked (1935 U/L; normal range, 22 to 198 U/L) within the first 24 hours of presentation and then trended down.

The Diagnosis

The patient’s sudden onset of symmetrical bilateral calf pain in the setting of an upper respiratory tract infection was extremely suspicious for benign acute childhood myositis (BACM). Lab work and radiologic evaluation were performed to rule out more ominous causes of refusal to bear weight. The suspicion of BACM was further validated by influenza B serology, an elevated CK, and a normal CRP.

While several infectious etiologies have been linked to benign acute childhood myositis, influenza B has the greatest association.

Discussion

BACM was first described by Lundberg in 1957.¹ The overall incidence and prevalence are unclear.² A viral prodrome involving rhinorrhea, low-grade fever, sore throat, cough, and malaise typically precedes bilateral calf pain by 3 days.^2-4 Myositis symptoms typically last for 4 days.³ While several infectious etiologies have been linked to this condition, influenza B has the greatest association.^5,6

 ❚ Patient population. BACM occurs predominately in school-aged children (6-8 years old) and has a male-to-female ratio of 2:1.^3,5,6 In a retrospective study of 219 children, BACM was strongly associated with male gender and ages 6 to 9 years.³ In another retrospective study of 54 children,80% of patients were male, and the mean age was 7.3 years.⁵

❚ Key symptoms and differential. The distinguishing feature of BACM is bilateral symmetric gastrocnemius-soleus tenderness.^2,4 Additionally, the lack of neurologic symptoms is an important differentiator, as long as refusal to bear weight is not mistaken for weakness.⁶ These features help to distinguish BACM from other items in the differential, including trauma, Guillain-Barre syndrome, osteomyelitis, malignancy, deep vein thrombosis, and inherited musculoskeletal disorders.²

Continue to: Labratory evaluation...

❚ Laboratory evaluation will often show mild neutropenia, thrombocytopenia, and mild elevation in CK.^7,8 CRP is typically normal.^4,7,9 In a retrospective study of 28 admissions for BACM from 2001 to 2012, common findings included leukopenia (35%), neutropenia (25%), and thrombocytopenia (21%). The median CK value was 4181 U/L.⁴ In another analysis of BACM cases, mean CK was 1872 U/L.⁵

❚ Biopsy is unnecessary; however, calf muscle samples from 11 of 12 children with suspected BACM due to influenza B infection were consistent with patchy necrosis without significant myositis.¹⁰

❚ Complications. Rhabdomyolysis, although rare, has been reported with BACM. In 1 analysis, 10 of 316 patients with influenza-associated myositis developed rhabdomyolysis; 8 experienced renal failure. Rhabdomyolysis was 4 times more likely to occur in girls, and 86% of cases were associated with influenza A.⁶ Common manifestations of rhabdomyolysis associated with influenza include diffuse myopathy, gross hematuria, and myoglobinuria.⁶

❚ Treatment is mainly supportive.^4,8,9 Antivirals typically are not indicated, as the bilateral calf pain manifests during the recovery phase of the illness.^4,9,11 BACM is self-limited and should resolve within 3 days of myositis manifestation.² Patients should follow up in 2 to 3 weeks to verify symptom resolution.²

If muscle pain, swelling, and tenderness worsen, further work-up is indicated. In more severe cases, including those involving renal failure, intensive care management and even dialysis may be necessary.^4,6

❚ Our patient was hospitalized due to fever in the setting of neutropenia. Ultimately, he was treated with acetaminophen and intravenous fluids for mild dehydration and elevated CK levels. He was discharged home after 3 days, at which time he had complete resolution of pain and was able to resume normal activities.

The Takeaway

Benign acute childhood myositis is a self-limited disorder with an excellent prognosis. It has a typical presentation and therefore should be a clinical diagnosis; however, investigative studies may be warranted to rule out more ominous causes. Reassurance to family that the condition should self-resolve in a few days is important. Close follow-up should be scheduled to ensure resolution of symptoms. 

CORRESPONDENCE

Nicholas A. Rathjen, DO, William Beaumont Army Medical Center, Department of Soldier and Family Care, 11335 SSG Sims Street, Fort Bliss, TX 79918; nicholas.a.rathjen@gmail. com

THE CASE

A 5-year-old previously healthy white boy presented to clinic with bilateral calf pain and refusal to bear weight since awakening that morning. Associated symptoms included a 3-day history of generalized fatigue, subjective fevers, cough, congestion, and rhinitis. The night prior to presentation, he showed no symptoms of gait abnormalities, muscle pain, or weakness. There was no history of similar symptoms, trauma, overexertion, foreign travel, or family history of musculoskeletal disease. He was fully immunized, except for the annual influenza vaccine. He was not taking any medications. This case occurred before the onset of the COVID-19 pandemic.

Objective findings included fever of 101 °F, refusal to bear weight, and symmetrical bilateral tenderness to palpation of the gastrocnemius-soleus complex. Pain was elicited with passive dorsiflexion. There was no erythema, edema, or sensory deficits, and the distal leg compartments were soft. There was normal range of motion of the hips, knees, and ankles. Dorsalis pedis pulses were 2+, and patella reflexes were 2/4 bilaterally.

Lab results included a white blood cell count of 2500/μL (normal range, 4500 to 11,000/μL);absolute neutrophil count, 900/μL (1500 to 8000/μL); platelet count, 131,000/μL (150,000 to 450,000/μL); creatine kinase level, 869 IU/L (22 to 198 U/L); and aspartate aminotransferase level, 116 U/L (8 to 33 U/L). A rapid influenza swab was positive for influenza B. Plain films of the bilateral hips and lower extremities were unremarkable. C-reactive protein (CRP) level, urinalysis, and renal function tests were within normal limits. Creatine kinase (CK) level peaked (1935 U/L; normal range, 22 to 198 U/L) within the first 24 hours of presentation and then trended down.

The Diagnosis

The patient’s sudden onset of symmetrical bilateral calf pain in the setting of an upper respiratory tract infection was extremely suspicious for benign acute childhood myositis (BACM). Lab work and radiologic evaluation were performed to rule out more ominous causes of refusal to bear weight. The suspicion of BACM was further validated by influenza B serology, an elevated CK, and a normal CRP.

While several infectious etiologies have been linked to benign acute childhood myositis, influenza B has the greatest association.

Discussion

BACM was first described by Lundberg in 1957.¹ The overall incidence and prevalence are unclear.² A viral prodrome involving rhinorrhea, low-grade fever, sore throat, cough, and malaise typically precedes bilateral calf pain by 3 days.^2-4 Myositis symptoms typically last for 4 days.³ While several infectious etiologies have been linked to this condition, influenza B has the greatest association.^5,6

 ❚ Patient population. BACM occurs predominately in school-aged children (6-8 years old) and has a male-to-female ratio of 2:1.^3,5,6 In a retrospective study of 219 children, BACM was strongly associated with male gender and ages 6 to 9 years.³ In another retrospective study of 54 children,80% of patients were male, and the mean age was 7.3 years.⁵

❚ Key symptoms and differential. The distinguishing feature of BACM is bilateral symmetric gastrocnemius-soleus tenderness.^2,4 Additionally, the lack of neurologic symptoms is an important differentiator, as long as refusal to bear weight is not mistaken for weakness.⁶ These features help to distinguish BACM from other items in the differential, including trauma, Guillain-Barre syndrome, osteomyelitis, malignancy, deep vein thrombosis, and inherited musculoskeletal disorders.²

Continue to: Labratory evaluation...

❚ Laboratory evaluation will often show mild neutropenia, thrombocytopenia, and mild elevation in CK.^7,8 CRP is typically normal.^4,7,9 In a retrospective study of 28 admissions for BACM from 2001 to 2012, common findings included leukopenia (35%), neutropenia (25%), and thrombocytopenia (21%). The median CK value was 4181 U/L.⁴ In another analysis of BACM cases, mean CK was 1872 U/L.⁵

❚ Biopsy is unnecessary; however, calf muscle samples from 11 of 12 children with suspected BACM due to influenza B infection were consistent with patchy necrosis without significant myositis.¹⁰

❚ Complications. Rhabdomyolysis, although rare, has been reported with BACM. In 1 analysis, 10 of 316 patients with influenza-associated myositis developed rhabdomyolysis; 8 experienced renal failure. Rhabdomyolysis was 4 times more likely to occur in girls, and 86% of cases were associated with influenza A.⁶ Common manifestations of rhabdomyolysis associated with influenza include diffuse myopathy, gross hematuria, and myoglobinuria.⁶

❚ Treatment is mainly supportive.^4,8,9 Antivirals typically are not indicated, as the bilateral calf pain manifests during the recovery phase of the illness.^4,9,11 BACM is self-limited and should resolve within 3 days of myositis manifestation.² Patients should follow up in 2 to 3 weeks to verify symptom resolution.²

If muscle pain, swelling, and tenderness worsen, further work-up is indicated. In more severe cases, including those involving renal failure, intensive care management and even dialysis may be necessary.^4,6

❚ Our patient was hospitalized due to fever in the setting of neutropenia. Ultimately, he was treated with acetaminophen and intravenous fluids for mild dehydration and elevated CK levels. He was discharged home after 3 days, at which time he had complete resolution of pain and was able to resume normal activities.

The Takeaway

Benign acute childhood myositis is a self-limited disorder with an excellent prognosis. It has a typical presentation and therefore should be a clinical diagnosis; however, investigative studies may be warranted to rule out more ominous causes. Reassurance to family that the condition should self-resolve in a few days is important. Close follow-up should be scheduled to ensure resolution of symptoms. 

CORRESPONDENCE

Nicholas A. Rathjen, DO, William Beaumont Army Medical Center, Department of Soldier and Family Care, 11335 SSG Sims Street, Fort Bliss, TX 79918; nicholas.a.rathjen@gmail. com

THE CASE

A 5-year-old previously healthy white boy presented to clinic with bilateral calf pain and refusal to bear weight since awakening that morning. Associated symptoms included a 3-day history of generalized fatigue, subjective fevers, cough, congestion, and rhinitis. The night prior to presentation, he showed no symptoms of gait abnormalities, muscle pain, or weakness. There was no history of similar symptoms, trauma, overexertion, foreign travel, or family history of musculoskeletal disease. He was fully immunized, except for the annual influenza vaccine. He was not taking any medications. This case occurred before the onset of the COVID-19 pandemic.

Objective findings included fever of 101 °F, refusal to bear weight, and symmetrical bilateral tenderness to palpation of the gastrocnemius-soleus complex. Pain was elicited with passive dorsiflexion. There was no erythema, edema, or sensory deficits, and the distal leg compartments were soft. There was normal range of motion of the hips, knees, and ankles. Dorsalis pedis pulses were 2+, and patella reflexes were 2/4 bilaterally.

Lab results included a white blood cell count of 2500/μL (normal range, 4500 to 11,000/μL);absolute neutrophil count, 900/μL (1500 to 8000/μL); platelet count, 131,000/μL (150,000 to 450,000/μL); creatine kinase level, 869 IU/L (22 to 198 U/L); and aspartate aminotransferase level, 116 U/L (8 to 33 U/L). A rapid influenza swab was positive for influenza B. Plain films of the bilateral hips and lower extremities were unremarkable. C-reactive protein (CRP) level, urinalysis, and renal function tests were within normal limits. Creatine kinase (CK) level peaked (1935 U/L; normal range, 22 to 198 U/L) within the first 24 hours of presentation and then trended down.

The Diagnosis

The patient’s sudden onset of symmetrical bilateral calf pain in the setting of an upper respiratory tract infection was extremely suspicious for benign acute childhood myositis (BACM). Lab work and radiologic evaluation were performed to rule out more ominous causes of refusal to bear weight. The suspicion of BACM was further validated by influenza B serology, an elevated CK, and a normal CRP.

While several infectious etiologies have been linked to benign acute childhood myositis, influenza B has the greatest association.

Discussion

BACM was first described by Lundberg in 1957.¹ The overall incidence and prevalence are unclear.² A viral prodrome involving rhinorrhea, low-grade fever, sore throat, cough, and malaise typically precedes bilateral calf pain by 3 days.^2-4 Myositis symptoms typically last for 4 days.³ While several infectious etiologies have been linked to this condition, influenza B has the greatest association.^5,6

 ❚ Patient population. BACM occurs predominately in school-aged children (6-8 years old) and has a male-to-female ratio of 2:1.^3,5,6 In a retrospective study of 219 children, BACM was strongly associated with male gender and ages 6 to 9 years.³ In another retrospective study of 54 children,80% of patients were male, and the mean age was 7.3 years.⁵

❚ Key symptoms and differential. The distinguishing feature of BACM is bilateral symmetric gastrocnemius-soleus tenderness.^2,4 Additionally, the lack of neurologic symptoms is an important differentiator, as long as refusal to bear weight is not mistaken for weakness.⁶ These features help to distinguish BACM from other items in the differential, including trauma, Guillain-Barre syndrome, osteomyelitis, malignancy, deep vein thrombosis, and inherited musculoskeletal disorders.²

Continue to: Labratory evaluation...

❚ Laboratory evaluation will often show mild neutropenia, thrombocytopenia, and mild elevation in CK.^7,8 CRP is typically normal.^4,7,9 In a retrospective study of 28 admissions for BACM from 2001 to 2012, common findings included leukopenia (35%), neutropenia (25%), and thrombocytopenia (21%). The median CK value was 4181 U/L.⁴ In another analysis of BACM cases, mean CK was 1872 U/L.⁵

❚ Biopsy is unnecessary; however, calf muscle samples from 11 of 12 children with suspected BACM due to influenza B infection were consistent with patchy necrosis without significant myositis.¹⁰

❚ Complications. Rhabdomyolysis, although rare, has been reported with BACM. In 1 analysis, 10 of 316 patients with influenza-associated myositis developed rhabdomyolysis; 8 experienced renal failure. Rhabdomyolysis was 4 times more likely to occur in girls, and 86% of cases were associated with influenza A.⁶ Common manifestations of rhabdomyolysis associated with influenza include diffuse myopathy, gross hematuria, and myoglobinuria.⁶

❚ Treatment is mainly supportive.^4,8,9 Antivirals typically are not indicated, as the bilateral calf pain manifests during the recovery phase of the illness.^4,9,11 BACM is self-limited and should resolve within 3 days of myositis manifestation.² Patients should follow up in 2 to 3 weeks to verify symptom resolution.²

If muscle pain, swelling, and tenderness worsen, further work-up is indicated. In more severe cases, including those involving renal failure, intensive care management and even dialysis may be necessary.^4,6

❚ Our patient was hospitalized due to fever in the setting of neutropenia. Ultimately, he was treated with acetaminophen and intravenous fluids for mild dehydration and elevated CK levels. He was discharged home after 3 days, at which time he had complete resolution of pain and was able to resume normal activities.

The Takeaway

Benign acute childhood myositis is a self-limited disorder with an excellent prognosis. It has a typical presentation and therefore should be a clinical diagnosis; however, investigative studies may be warranted to rule out more ominous causes. Reassurance to family that the condition should self-resolve in a few days is important. Close follow-up should be scheduled to ensure resolution of symptoms. 

CORRESPONDENCE

Nicholas A. Rathjen, DO, William Beaumont Army Medical Center, Department of Soldier and Family Care, 11335 SSG Sims Street, Fort Bliss, TX 79918; nicholas.a.rathjen@gmail. com