Clinical Edge Journal Scan

Appropriate assessment of MSK symptoms and signs by dermatologists may lead to more appropriate referral to rheumatologists. MSUS is being increasingly explored for early identification of PsA. A handheld, chip-based ultrasound device (HHUD) is a novel promising instrument that can be easily implemented in clinical practice. In a prospective study including 140 patients with psoriasis who presented to dermatologists with arthralgia. Grobelski and colleagues screened for PsA using medical history, CE, and the German Psoriasis Arthritis Diagnostic PsA screening questionnaire (GEPARD) paired with MSUS examination of up to three painful joints by trained dermatologists. Nineteen patients (13.6%) were diagnosed with PsA by rheumatologists. Interestingly, in 45 of the 46 patients the preliminary diagnosis of PsA was revised to "no PsA" after MSUS. The addition of MSUS changed the sensitivity and specificity of early PsA screening strategy from 88.2% and 54.4% to 70.6% and 90.4%, respectively. The positive predictive value increased to 56.5% from 25.4% after MSUS. Thus, the use of a quick MSUS using HHUD may lead to more accurate referral to rheumatologists. The challenge is seamless integration of MSUS into busy dermatology practices.

The goal of PsA treatment is to achieve a state of remission or low disease activity. Criteria for minimal disease activity (MDA) have been established. Achieving MDA leads to better health-related quality of life (HRQOL), as well as less joint damage. In a prospective cohort study that included 240 patients with newly diagnosed disease-modifying antirheumatic drug-naive PsA, Snoeck Henkemans and colleagues demonstrate that failure to achieve MDA in the first year after the diagnosis of PsA was associated with worse HRQOL and health status, functional impairment, fatigue, pain, and higher anxiety and depression. Compared with patients who achieved sustained MDA in the first year after diagnosis, those who did not achieve MDA had higher scores for pain, fatigue, and functional ability and higher anxiety and depression during follow-up, which persisted despite treatment intensification. Thus, implementation of treat-to-target strategies with the aim of achieving sustained MDA within 1 year of diagnosis is likely to have better long-term benefits in this lifelong disease.

Another study emphasized the need for early treatment to improve long-term outcomes. In a post hoc analysis of two phase 3 trials including 1554 patients with PsA who received 300-mg or 150-mg secukinumab with or without a loading dose, Mease and colleagues showed that high baseline radiographic damage reduced the likelihood of achieving MDA.

Overall, these studies indicate that early diagnosis and treatment prior to developing joint damage with the aim to achieve sustained MDA within a year will lead to better long-term outcome for patients with PsA.

Appropriate assessment of MSK symptoms and signs by dermatologists may lead to more appropriate referral to rheumatologists. MSUS is being increasingly explored for early identification of PsA. A handheld, chip-based ultrasound device (HHUD) is a novel promising instrument that can be easily implemented in clinical practice. In a prospective study including 140 patients with psoriasis who presented to dermatologists with arthralgia. Grobelski and colleagues screened for PsA using medical history, CE, and the German Psoriasis Arthritis Diagnostic PsA screening questionnaire (GEPARD) paired with MSUS examination of up to three painful joints by trained dermatologists. Nineteen patients (13.6%) were diagnosed with PsA by rheumatologists. Interestingly, in 45 of the 46 patients the preliminary diagnosis of PsA was revised to "no PsA" after MSUS. The addition of MSUS changed the sensitivity and specificity of early PsA screening strategy from 88.2% and 54.4% to 70.6% and 90.4%, respectively. The positive predictive value increased to 56.5% from 25.4% after MSUS. Thus, the use of a quick MSUS using HHUD may lead to more accurate referral to rheumatologists. The challenge is seamless integration of MSUS into busy dermatology practices.

The goal of PsA treatment is to achieve a state of remission or low disease activity. Criteria for minimal disease activity (MDA) have been established. Achieving MDA leads to better health-related quality of life (HRQOL), as well as less joint damage. In a prospective cohort study that included 240 patients with newly diagnosed disease-modifying antirheumatic drug-naive PsA, Snoeck Henkemans and colleagues demonstrate that failure to achieve MDA in the first year after the diagnosis of PsA was associated with worse HRQOL and health status, functional impairment, fatigue, pain, and higher anxiety and depression. Compared with patients who achieved sustained MDA in the first year after diagnosis, those who did not achieve MDA had higher scores for pain, fatigue, and functional ability and higher anxiety and depression during follow-up, which persisted despite treatment intensification. Thus, implementation of treat-to-target strategies with the aim of achieving sustained MDA within 1 year of diagnosis is likely to have better long-term benefits in this lifelong disease.

Another study emphasized the need for early treatment to improve long-term outcomes. In a post hoc analysis of two phase 3 trials including 1554 patients with PsA who received 300-mg or 150-mg secukinumab with or without a loading dose, Mease and colleagues showed that high baseline radiographic damage reduced the likelihood of achieving MDA.

Overall, these studies indicate that early diagnosis and treatment prior to developing joint damage with the aim to achieve sustained MDA within a year will lead to better long-term outcome for patients with PsA.

Appropriate assessment of MSK symptoms and signs by dermatologists may lead to more appropriate referral to rheumatologists. MSUS is being increasingly explored for early identification of PsA. A handheld, chip-based ultrasound device (HHUD) is a novel promising instrument that can be easily implemented in clinical practice. In a prospective study including 140 patients with psoriasis who presented to dermatologists with arthralgia. Grobelski and colleagues screened for PsA using medical history, CE, and the German Psoriasis Arthritis Diagnostic PsA screening questionnaire (GEPARD) paired with MSUS examination of up to three painful joints by trained dermatologists. Nineteen patients (13.6%) were diagnosed with PsA by rheumatologists. Interestingly, in 45 of the 46 patients the preliminary diagnosis of PsA was revised to "no PsA" after MSUS. The addition of MSUS changed the sensitivity and specificity of early PsA screening strategy from 88.2% and 54.4% to 70.6% and 90.4%, respectively. The positive predictive value increased to 56.5% from 25.4% after MSUS. Thus, the use of a quick MSUS using HHUD may lead to more accurate referral to rheumatologists. The challenge is seamless integration of MSUS into busy dermatology practices.

The goal of PsA treatment is to achieve a state of remission or low disease activity. Criteria for minimal disease activity (MDA) have been established. Achieving MDA leads to better health-related quality of life (HRQOL), as well as less joint damage. In a prospective cohort study that included 240 patients with newly diagnosed disease-modifying antirheumatic drug-naive PsA, Snoeck Henkemans and colleagues demonstrate that failure to achieve MDA in the first year after the diagnosis of PsA was associated with worse HRQOL and health status, functional impairment, fatigue, pain, and higher anxiety and depression. Compared with patients who achieved sustained MDA in the first year after diagnosis, those who did not achieve MDA had higher scores for pain, fatigue, and functional ability and higher anxiety and depression during follow-up, which persisted despite treatment intensification. Thus, implementation of treat-to-target strategies with the aim of achieving sustained MDA within 1 year of diagnosis is likely to have better long-term benefits in this lifelong disease.

Another study emphasized the need for early treatment to improve long-term outcomes. In a post hoc analysis of two phase 3 trials including 1554 patients with PsA who received 300-mg or 150-mg secukinumab with or without a loading dose, Mease and colleagues showed that high baseline radiographic damage reduced the likelihood of achieving MDA.

Overall, these studies indicate that early diagnosis and treatment prior to developing joint damage with the aim to achieve sustained MDA within a year will lead to better long-term outcome for patients with PsA.

The elevated risk for recurrence in young women with HR+ early breast cancer highlights the importance of aggressive endocrine therapy in the majority of patients in this population. Examples of approaches to maximize endocrine therapy benefit include the addition of ovarian suppression to either tamoxifen or an aromatase inhibitor (AI) as well as an extended duration of adjuvant endocrine therapy.^4,5 Among 3047 premenopausal women included in SOFT study, at 12 years follow-up, the addition of ovarian function suppression (OFS) to tamoxifen significantly improved disease-free survival (DFS) compared with tamoxifen alone (hazard ratio 0.82; P = .03) with a more pronounced DFS benefit with exemestane plus OFS compared with tamoxifen (hazard ratio 0.69) (Francis et al). In the HER2- subgroup, those who received prior chemotherapy had 12-year OFS rates of 78.8% with tamoxifen, 81.1% with tamoxifen plus OFS and 84.4% with exemestane plus OFS. Furthermore, in the HER2- subgroup, women younger than 35 years had absolute improvements in 12-year OS of 9.1% with tamoxifen plus OFS and 16.5% with exemestane plus OFS compared with tamoxifen. These updated results provide further support for OFS added to tamoxifen or an AI (with more benefit seen with an AI) in the treatment of HR+ early breast cancer in young women who are at high risk for recurrence. Longer follow-up will be important to better define the treatment effect considering recurrence patterns for this subtype of breast cancer.

Various guidelines recommend the use of adjuvant bisphosphonates for postmenopausal patients with early breast cancer on the basis of disease-free and bone metastasis-free survival benefits.⁶ A regimen of zolendronic acid every 6 months for 3 years is commonly used in clinical practice. A substudy of ABCSG-12, including 725 premenopausal patients with HR+ early breast cancer on ovarian suppression randomly assigned to receive tamoxifen or anastrozole with or without zolendronic acid every 6 months, investigated the effect of shorter duration of bisphosphonate therapy on breast cancer outcomes (Beltran-Bless et al). After a median follow-up of 96 months, there was no statistically significant difference in DFS (hazard ratio 0.88; log-rank P = .642) or OS (stratified hazard ratio 1.16; log-rank P = .796) between patients who received ≤6 or ≥7 infusions. Rates of adverse events were increased in the patients who received ≥7 or ≤6 infusions (arthralgia, 20.1% vs 12.4%; nausea, 12.8% vs 7.3%; bone pain, 41.6% vs 34.9%). Modifications to adjuvant breast cancer regimens that can provide more ease for patients with less toxicity while maintaining efficacy are greatly desired to simultaneously support quality of life and disease outcomes.

Additional References

1. Swain SM, Baselga J, Kim SB, et al; for the CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372:724-734. Doi: 10.1056/NEJMoa1413513
2. Miles D, Ciruelos E, Schneeweiss A, et al; for the PERUSE investigators. Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication. Ann Oncol. 2021;32:1245-1255. Doi: 10.1016/j.annonc.2021.06.024
3. Hua X, Bi X-W, Zhao J-L, et al; for the South China Breast Cancer Group (SCBCG). Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for patients with hormone receptor-positive and HER2-positive metastatic breast cancer (SYSUCC-002). Clin Cancer Res. 2022;28:637-645. Doi: 10.1158/1078-0432.CCR-21-3435
4. Kim H-A, Lee JW, Nam SJ, et al; for the Korean Breast Cancer Study Group. Adding ovarian suppression to tamoxifen for premenopausal breast Cancer: a randomized phase III trial. J Clin Oncol. 2020;38:434-443. Doi: 10.1200/JCO.19.00126
5. Davies C, Pan H, Godwin J, et al; for the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381:805-816. Doi: 10.1016/S0140-6736(12)61963-1
6. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386:1353-1361. Doi: 10.1016/S0140-6736(15)60908-4

The elevated risk for recurrence in young women with HR+ early breast cancer highlights the importance of aggressive endocrine therapy in the majority of patients in this population. Examples of approaches to maximize endocrine therapy benefit include the addition of ovarian suppression to either tamoxifen or an aromatase inhibitor (AI) as well as an extended duration of adjuvant endocrine therapy.^4,5 Among 3047 premenopausal women included in SOFT study, at 12 years follow-up, the addition of ovarian function suppression (OFS) to tamoxifen significantly improved disease-free survival (DFS) compared with tamoxifen alone (hazard ratio 0.82; P = .03) with a more pronounced DFS benefit with exemestane plus OFS compared with tamoxifen (hazard ratio 0.69) (Francis et al). In the HER2- subgroup, those who received prior chemotherapy had 12-year OFS rates of 78.8% with tamoxifen, 81.1% with tamoxifen plus OFS and 84.4% with exemestane plus OFS. Furthermore, in the HER2- subgroup, women younger than 35 years had absolute improvements in 12-year OS of 9.1% with tamoxifen plus OFS and 16.5% with exemestane plus OFS compared with tamoxifen. These updated results provide further support for OFS added to tamoxifen or an AI (with more benefit seen with an AI) in the treatment of HR+ early breast cancer in young women who are at high risk for recurrence. Longer follow-up will be important to better define the treatment effect considering recurrence patterns for this subtype of breast cancer.

Various guidelines recommend the use of adjuvant bisphosphonates for postmenopausal patients with early breast cancer on the basis of disease-free and bone metastasis-free survival benefits.⁶ A regimen of zolendronic acid every 6 months for 3 years is commonly used in clinical practice. A substudy of ABCSG-12, including 725 premenopausal patients with HR+ early breast cancer on ovarian suppression randomly assigned to receive tamoxifen or anastrozole with or without zolendronic acid every 6 months, investigated the effect of shorter duration of bisphosphonate therapy on breast cancer outcomes (Beltran-Bless et al). After a median follow-up of 96 months, there was no statistically significant difference in DFS (hazard ratio 0.88; log-rank P = .642) or OS (stratified hazard ratio 1.16; log-rank P = .796) between patients who received ≤6 or ≥7 infusions. Rates of adverse events were increased in the patients who received ≥7 or ≤6 infusions (arthralgia, 20.1% vs 12.4%; nausea, 12.8% vs 7.3%; bone pain, 41.6% vs 34.9%). Modifications to adjuvant breast cancer regimens that can provide more ease for patients with less toxicity while maintaining efficacy are greatly desired to simultaneously support quality of life and disease outcomes.

Additional References

1. Swain SM, Baselga J, Kim SB, et al; for the CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372:724-734. Doi: 10.1056/NEJMoa1413513
2. Miles D, Ciruelos E, Schneeweiss A, et al; for the PERUSE investigators. Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication. Ann Oncol. 2021;32:1245-1255. Doi: 10.1016/j.annonc.2021.06.024
3. Hua X, Bi X-W, Zhao J-L, et al; for the South China Breast Cancer Group (SCBCG). Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for patients with hormone receptor-positive and HER2-positive metastatic breast cancer (SYSUCC-002). Clin Cancer Res. 2022;28:637-645. Doi: 10.1158/1078-0432.CCR-21-3435
4. Kim H-A, Lee JW, Nam SJ, et al; for the Korean Breast Cancer Study Group. Adding ovarian suppression to tamoxifen for premenopausal breast Cancer: a randomized phase III trial. J Clin Oncol. 2020;38:434-443. Doi: 10.1200/JCO.19.00126
5. Davies C, Pan H, Godwin J, et al; for the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381:805-816. Doi: 10.1016/S0140-6736(12)61963-1
6. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386:1353-1361. Doi: 10.1016/S0140-6736(15)60908-4

The elevated risk for recurrence in young women with HR+ early breast cancer highlights the importance of aggressive endocrine therapy in the majority of patients in this population. Examples of approaches to maximize endocrine therapy benefit include the addition of ovarian suppression to either tamoxifen or an aromatase inhibitor (AI) as well as an extended duration of adjuvant endocrine therapy.^4,5 Among 3047 premenopausal women included in SOFT study, at 12 years follow-up, the addition of ovarian function suppression (OFS) to tamoxifen significantly improved disease-free survival (DFS) compared with tamoxifen alone (hazard ratio 0.82; P = .03) with a more pronounced DFS benefit with exemestane plus OFS compared with tamoxifen (hazard ratio 0.69) (Francis et al). In the HER2- subgroup, those who received prior chemotherapy had 12-year OFS rates of 78.8% with tamoxifen, 81.1% with tamoxifen plus OFS and 84.4% with exemestane plus OFS. Furthermore, in the HER2- subgroup, women younger than 35 years had absolute improvements in 12-year OS of 9.1% with tamoxifen plus OFS and 16.5% with exemestane plus OFS compared with tamoxifen. These updated results provide further support for OFS added to tamoxifen or an AI (with more benefit seen with an AI) in the treatment of HR+ early breast cancer in young women who are at high risk for recurrence. Longer follow-up will be important to better define the treatment effect considering recurrence patterns for this subtype of breast cancer.

Various guidelines recommend the use of adjuvant bisphosphonates for postmenopausal patients with early breast cancer on the basis of disease-free and bone metastasis-free survival benefits.⁶ A regimen of zolendronic acid every 6 months for 3 years is commonly used in clinical practice. A substudy of ABCSG-12, including 725 premenopausal patients with HR+ early breast cancer on ovarian suppression randomly assigned to receive tamoxifen or anastrozole with or without zolendronic acid every 6 months, investigated the effect of shorter duration of bisphosphonate therapy on breast cancer outcomes (Beltran-Bless et al). After a median follow-up of 96 months, there was no statistically significant difference in DFS (hazard ratio 0.88; log-rank P = .642) or OS (stratified hazard ratio 1.16; log-rank P = .796) between patients who received ≤6 or ≥7 infusions. Rates of adverse events were increased in the patients who received ≥7 or ≤6 infusions (arthralgia, 20.1% vs 12.4%; nausea, 12.8% vs 7.3%; bone pain, 41.6% vs 34.9%). Modifications to adjuvant breast cancer regimens that can provide more ease for patients with less toxicity while maintaining efficacy are greatly desired to simultaneously support quality of life and disease outcomes.

Additional References

1. Swain SM, Baselga J, Kim SB, et al; for the CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372:724-734. Doi: 10.1056/NEJMoa1413513
2. Miles D, Ciruelos E, Schneeweiss A, et al; for the PERUSE investigators. Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication. Ann Oncol. 2021;32:1245-1255. Doi: 10.1016/j.annonc.2021.06.024
3. Hua X, Bi X-W, Zhao J-L, et al; for the South China Breast Cancer Group (SCBCG). Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for patients with hormone receptor-positive and HER2-positive metastatic breast cancer (SYSUCC-002). Clin Cancer Res. 2022;28:637-645. Doi: 10.1158/1078-0432.CCR-21-3435
4. Kim H-A, Lee JW, Nam SJ, et al; for the Korean Breast Cancer Study Group. Adding ovarian suppression to tamoxifen for premenopausal breast Cancer: a randomized phase III trial. J Clin Oncol. 2020;38:434-443. Doi: 10.1200/JCO.19.00126
5. Davies C, Pan H, Godwin J, et al; for the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381:805-816. Doi: 10.1016/S0140-6736(12)61963-1
6. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386:1353-1361. Doi: 10.1016/S0140-6736(15)60908-4

I love registries! With large numbers of participants, registries can be very helpful to identify rare side effects and to assess the efficacy and safety of medications in populations that may not be fully represented in clinical trials. I also love dupilumab; it was revolutionary in the management of patients with AD.

Vittrup and colleagues have created a registry of 347 participants treated with dupilumab. This does not yet have the large number of participants needed to identify new issues that wouldn't have been detected in clinical trials, but the study is informative about real-life use. The dramatic improvement in the Eczema Area and Severity Index (EASI) score is consistent with the high efficacy of dupilumab. The high rate of treatment persistence is also consistent with dupilumab being a very effective and safe treatment (because if the drug wasn't working well or was causing a severe problem, patients would probably stop the treatment). Though the study reported persistent head and neck involvement, the residual involvement may be quite minimal.

The EASI-75 and Investigator Global Assessment response rates reported in dupilumab trials underestimate the value of this drug. With a 2-year persistence rate of nearly 90%, it's clear that dupilumab is making a huge difference in the lives of patients with AD.

Fatigue is a fascinating issue in AD. We might wonder if all the inflammation in patients with AD would directly cause fatigue. Almost certainly all the itching in AD adversely affects sleep and would cause tremendous fatigue. It surprised me that most of the children in the study by Rangel and colleagues were reported as having no or mild fatigue; severe fatigue was very uncommon. It leaves me wondering whether the assessments of fatigue fully capture what's happening. Also, since the fatigue score was reported by the parents, I (as the parent of a child with AD) am wondering whether the parents were projecting, with the score more reflective of the parents' fatigue than with that of the child; alternatively, perhaps the child's hyperactivity leaves parents thinking there is no fatigue when there actually is (and possibly even causing the perceived hyperactivity).

The lack of a control group without AD is another major limitation in our ability to interpret the study findings. Is fatigue more common or less common in children with AD than in children without AD? I cannot tell from these findings. Does fatigue warrant, as the authors suggest, more attention in clinical practice? I don't know. If we are already treating our patients based on patients' global impressions of how they are doing — combined, of course, with our observations of their objective disease severity — I'm not sure how asking about fatigue would change anything, even if future studies were to definitively show that AD is associated with fatigue.

I hate new drugs (well, maybe not hate, but I worry about unknown long-term risks). Clinical trials that help a drug get approved can tell us a lot about a drug's efficacy, but these studies are generally limited in what they tell us about a drug's safety. Clinical trials are generally not powered enough (not enough participants and not followed for long enough) to be informative about rare risks. I love long-term studies of new drugs in large numbers of people because those studies can be very reassuring about the risks of medications. Studying nearly 10,000 patients for 5 years is quite reassuring, confirming my impression that dupilumab has a remarkable, excellent safety profile (Owji et al). Blocking interleukin 4 and interleukin 13 seems to be very specific to AD. Finding no association to cancer is what I would have expected; being able to share this information with patients is likely to be reassuring to them.

Oh, lord help me, another study that claims we should change our disease management because they've identified an increased risk for something. When you compare 70,000 patients with 270,000 controls, you have huge power to detect statistically significant associations of no clinical consequence. Let's assume for the moment that the detected association the authors found between AD and juvenile idiopathic arthritis (JIA) is real. The odds ratio is 2; the odds ratio for smoking causing cancer is on the order of 100.

In this study, over 99% of individuals in both AD and control groups did not have JIA. The difference between rates of JIA in patients with AD compared with controls was 0.3%! The authors conclude "it is important to inquire actively about symptoms not directly linked to the patients' skin disease"; based on the findings of this study, I would conclude that we don't need to worry about JIA in patients with AD even if there is a (marginally) higher prevalence of JIA in this group.

I love registries! With large numbers of participants, registries can be very helpful to identify rare side effects and to assess the efficacy and safety of medications in populations that may not be fully represented in clinical trials. I also love dupilumab; it was revolutionary in the management of patients with AD.

Vittrup and colleagues have created a registry of 347 participants treated with dupilumab. This does not yet have the large number of participants needed to identify new issues that wouldn't have been detected in clinical trials, but the study is informative about real-life use. The dramatic improvement in the Eczema Area and Severity Index (EASI) score is consistent with the high efficacy of dupilumab. The high rate of treatment persistence is also consistent with dupilumab being a very effective and safe treatment (because if the drug wasn't working well or was causing a severe problem, patients would probably stop the treatment). Though the study reported persistent head and neck involvement, the residual involvement may be quite minimal.

The EASI-75 and Investigator Global Assessment response rates reported in dupilumab trials underestimate the value of this drug. With a 2-year persistence rate of nearly 90%, it's clear that dupilumab is making a huge difference in the lives of patients with AD.

Fatigue is a fascinating issue in AD. We might wonder if all the inflammation in patients with AD would directly cause fatigue. Almost certainly all the itching in AD adversely affects sleep and would cause tremendous fatigue. It surprised me that most of the children in the study by Rangel and colleagues were reported as having no or mild fatigue; severe fatigue was very uncommon. It leaves me wondering whether the assessments of fatigue fully capture what's happening. Also, since the fatigue score was reported by the parents, I (as the parent of a child with AD) am wondering whether the parents were projecting, with the score more reflective of the parents' fatigue than with that of the child; alternatively, perhaps the child's hyperactivity leaves parents thinking there is no fatigue when there actually is (and possibly even causing the perceived hyperactivity).

The lack of a control group without AD is another major limitation in our ability to interpret the study findings. Is fatigue more common or less common in children with AD than in children without AD? I cannot tell from these findings. Does fatigue warrant, as the authors suggest, more attention in clinical practice? I don't know. If we are already treating our patients based on patients' global impressions of how they are doing — combined, of course, with our observations of their objective disease severity — I'm not sure how asking about fatigue would change anything, even if future studies were to definitively show that AD is associated with fatigue.

I hate new drugs (well, maybe not hate, but I worry about unknown long-term risks). Clinical trials that help a drug get approved can tell us a lot about a drug's efficacy, but these studies are generally limited in what they tell us about a drug's safety. Clinical trials are generally not powered enough (not enough participants and not followed for long enough) to be informative about rare risks. I love long-term studies of new drugs in large numbers of people because those studies can be very reassuring about the risks of medications. Studying nearly 10,000 patients for 5 years is quite reassuring, confirming my impression that dupilumab has a remarkable, excellent safety profile (Owji et al). Blocking interleukin 4 and interleukin 13 seems to be very specific to AD. Finding no association to cancer is what I would have expected; being able to share this information with patients is likely to be reassuring to them.

Oh, lord help me, another study that claims we should change our disease management because they've identified an increased risk for something. When you compare 70,000 patients with 270,000 controls, you have huge power to detect statistically significant associations of no clinical consequence. Let's assume for the moment that the detected association the authors found between AD and juvenile idiopathic arthritis (JIA) is real. The odds ratio is 2; the odds ratio for smoking causing cancer is on the order of 100.

In this study, over 99% of individuals in both AD and control groups did not have JIA. The difference between rates of JIA in patients with AD compared with controls was 0.3%! The authors conclude "it is important to inquire actively about symptoms not directly linked to the patients' skin disease"; based on the findings of this study, I would conclude that we don't need to worry about JIA in patients with AD even if there is a (marginally) higher prevalence of JIA in this group.

I love registries! With large numbers of participants, registries can be very helpful to identify rare side effects and to assess the efficacy and safety of medications in populations that may not be fully represented in clinical trials. I also love dupilumab; it was revolutionary in the management of patients with AD.

Vittrup and colleagues have created a registry of 347 participants treated with dupilumab. This does not yet have the large number of participants needed to identify new issues that wouldn't have been detected in clinical trials, but the study is informative about real-life use. The dramatic improvement in the Eczema Area and Severity Index (EASI) score is consistent with the high efficacy of dupilumab. The high rate of treatment persistence is also consistent with dupilumab being a very effective and safe treatment (because if the drug wasn't working well or was causing a severe problem, patients would probably stop the treatment). Though the study reported persistent head and neck involvement, the residual involvement may be quite minimal.

The EASI-75 and Investigator Global Assessment response rates reported in dupilumab trials underestimate the value of this drug. With a 2-year persistence rate of nearly 90%, it's clear that dupilumab is making a huge difference in the lives of patients with AD.

Fatigue is a fascinating issue in AD. We might wonder if all the inflammation in patients with AD would directly cause fatigue. Almost certainly all the itching in AD adversely affects sleep and would cause tremendous fatigue. It surprised me that most of the children in the study by Rangel and colleagues were reported as having no or mild fatigue; severe fatigue was very uncommon. It leaves me wondering whether the assessments of fatigue fully capture what's happening. Also, since the fatigue score was reported by the parents, I (as the parent of a child with AD) am wondering whether the parents were projecting, with the score more reflective of the parents' fatigue than with that of the child; alternatively, perhaps the child's hyperactivity leaves parents thinking there is no fatigue when there actually is (and possibly even causing the perceived hyperactivity).

The lack of a control group without AD is another major limitation in our ability to interpret the study findings. Is fatigue more common or less common in children with AD than in children without AD? I cannot tell from these findings. Does fatigue warrant, as the authors suggest, more attention in clinical practice? I don't know. If we are already treating our patients based on patients' global impressions of how they are doing — combined, of course, with our observations of their objective disease severity — I'm not sure how asking about fatigue would change anything, even if future studies were to definitively show that AD is associated with fatigue.

I hate new drugs (well, maybe not hate, but I worry about unknown long-term risks). Clinical trials that help a drug get approved can tell us a lot about a drug's efficacy, but these studies are generally limited in what they tell us about a drug's safety. Clinical trials are generally not powered enough (not enough participants and not followed for long enough) to be informative about rare risks. I love long-term studies of new drugs in large numbers of people because those studies can be very reassuring about the risks of medications. Studying nearly 10,000 patients for 5 years is quite reassuring, confirming my impression that dupilumab has a remarkable, excellent safety profile (Owji et al). Blocking interleukin 4 and interleukin 13 seems to be very specific to AD. Finding no association to cancer is what I would have expected; being able to share this information with patients is likely to be reassuring to them.

Oh, lord help me, another study that claims we should change our disease management because they've identified an increased risk for something. When you compare 70,000 patients with 270,000 controls, you have huge power to detect statistically significant associations of no clinical consequence. Let's assume for the moment that the detected association the authors found between AD and juvenile idiopathic arthritis (JIA) is real. The odds ratio is 2; the odds ratio for smoking causing cancer is on the order of 100.

In this study, over 99% of individuals in both AD and control groups did not have JIA. The difference between rates of JIA in patients with AD compared with controls was 0.3%! The authors conclude "it is important to inquire actively about symptoms not directly linked to the patients' skin disease"; based on the findings of this study, I would conclude that we don't need to worry about JIA in patients with AD even if there is a (marginally) higher prevalence of JIA in this group.

Key clinical point: The presence of metabolic syndromes (MetS) worsened survival outcomes and increased disease recurrence risk in patients with breast cancer (BC) who received neoadjuvant chemotherapy (NAC).

Major finding: The MetS group had a significantly lower likelihood of achieving pathological complete response than the non-MetS group (odds ratio [OR] 0.316; P  =  .028), with the risk for death (OR 2.587; P  =  .004) and disease recurrence (OR 2.228; P  =  .007) being significantly higher in patients with vs without MetS.

Study details: Findings are from a retrospective study including 221 women with BC who received preoperative NAC, of which 22.2% of patients were included in the MetS group.

Disclosures: This study was supported by the Beijing Medical Award Foundation. The authors declared no conflicts of interest.

Source: Zhou Z et al. Metabolic syndrome is a risk factor for breast cancer patients receiving neoadjuvant chemotherapy: A case-control study. Front Oncol. 2023;12:1080054 (Jan 4). Doi: 10.3389/fonc.2022.1080054

Key clinical point: The presence of metabolic syndromes (MetS) worsened survival outcomes and increased disease recurrence risk in patients with breast cancer (BC) who received neoadjuvant chemotherapy (NAC).

Major finding: The MetS group had a significantly lower likelihood of achieving pathological complete response than the non-MetS group (odds ratio [OR] 0.316; P  =  .028), with the risk for death (OR 2.587; P  =  .004) and disease recurrence (OR 2.228; P  =  .007) being significantly higher in patients with vs without MetS.

Study details: Findings are from a retrospective study including 221 women with BC who received preoperative NAC, of which 22.2% of patients were included in the MetS group.

Disclosures: This study was supported by the Beijing Medical Award Foundation. The authors declared no conflicts of interest.

Source: Zhou Z et al. Metabolic syndrome is a risk factor for breast cancer patients receiving neoadjuvant chemotherapy: A case-control study. Front Oncol. 2023;12:1080054 (Jan 4). Doi: 10.3389/fonc.2022.1080054

Key clinical point: The presence of metabolic syndromes (MetS) worsened survival outcomes and increased disease recurrence risk in patients with breast cancer (BC) who received neoadjuvant chemotherapy (NAC).

Major finding: The MetS group had a significantly lower likelihood of achieving pathological complete response than the non-MetS group (odds ratio [OR] 0.316; P  =  .028), with the risk for death (OR 2.587; P  =  .004) and disease recurrence (OR 2.228; P  =  .007) being significantly higher in patients with vs without MetS.

Study details: Findings are from a retrospective study including 221 women with BC who received preoperative NAC, of which 22.2% of patients were included in the MetS group.

Disclosures: This study was supported by the Beijing Medical Award Foundation. The authors declared no conflicts of interest.

Source: Zhou Z et al. Metabolic syndrome is a risk factor for breast cancer patients receiving neoadjuvant chemotherapy: A case-control study. Front Oncol. 2023;12:1080054 (Jan 4). Doi: 10.3389/fonc.2022.1080054

Key clinical point: Recent phase 2 trials have recommended a 2-weekly schedule of pegylated liposomal doxorubicin (PLD) in patients with heavily treated metastatic breast cancer (BC); however, it failed to demonstrate any advantage in terms of efficacy or safety over the registered 4-weekly regimen of PLD.

Major finding: The median progression-free survival was 3.0 and 3.4 months in the 2-weekly and 4-weekly PLD schedule groups, respectively, with a weighted hazard ratio of 1.12 (P  =  .54). The rate of adverse events also appeared comparable between both the groups.

Study details: Findings are from a retrospective study including 191 heavily pretreated patients with metastatic BC who received a 2-weekly (n = 95) or the registered 4-weekly (n = 96) schedule of PLD.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Bischoff H et al. A propensity score-weighted study comparing a two- versus four-weekly pegylated liposomal doxorubicin regimen in metastatic breast cancer. Breast Cancer Res Treat. 2022 (Dec 23). Doi: 10.1007/s10549-022-06844-5

Key clinical point: Recent phase 2 trials have recommended a 2-weekly schedule of pegylated liposomal doxorubicin (PLD) in patients with heavily treated metastatic breast cancer (BC); however, it failed to demonstrate any advantage in terms of efficacy or safety over the registered 4-weekly regimen of PLD.

Major finding: The median progression-free survival was 3.0 and 3.4 months in the 2-weekly and 4-weekly PLD schedule groups, respectively, with a weighted hazard ratio of 1.12 (P  =  .54). The rate of adverse events also appeared comparable between both the groups.

Study details: Findings are from a retrospective study including 191 heavily pretreated patients with metastatic BC who received a 2-weekly (n = 95) or the registered 4-weekly (n = 96) schedule of PLD.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Bischoff H et al. A propensity score-weighted study comparing a two- versus four-weekly pegylated liposomal doxorubicin regimen in metastatic breast cancer. Breast Cancer Res Treat. 2022 (Dec 23). Doi: 10.1007/s10549-022-06844-5

Key clinical point: Recent phase 2 trials have recommended a 2-weekly schedule of pegylated liposomal doxorubicin (PLD) in patients with heavily treated metastatic breast cancer (BC); however, it failed to demonstrate any advantage in terms of efficacy or safety over the registered 4-weekly regimen of PLD.

Major finding: The median progression-free survival was 3.0 and 3.4 months in the 2-weekly and 4-weekly PLD schedule groups, respectively, with a weighted hazard ratio of 1.12 (P  =  .54). The rate of adverse events also appeared comparable between both the groups.

Study details: Findings are from a retrospective study including 191 heavily pretreated patients with metastatic BC who received a 2-weekly (n = 95) or the registered 4-weekly (n = 96) schedule of PLD.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Bischoff H et al. A propensity score-weighted study comparing a two- versus four-weekly pegylated liposomal doxorubicin regimen in metastatic breast cancer. Breast Cancer Res Treat. 2022 (Dec 23). Doi: 10.1007/s10549-022-06844-5

Key clinical point: Autologous fat grafting (AFG) in the second stage of a 2-stage prosthetic breast reconstruction was linked to a higher risk for breast cancer (BC) recurrence when performed within a year after mastectomy.

Major finding: Patients who did vs did not undergo AFG within 1 year after the primary operation had a significantly increased risk for disease recurrence (hazard ratio 5.701; 95% CI 1.164-27.927). However, delaying the fat grafting beyond 12 months after mastectomy did not affect survival outcomes.

Study details: Findings are from a retrospective cohort study including 267 patients with unilateral invasive BC who underwent total mastectomy and immediate tissue-expander-based reconstruction, of which 203 patients underwent the second-stage operation within 12 months of mastectomy and 64 patients underwent the operation after 12 months of mastectomy.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Lee KT et al. Association of fat graft with breast cancer recurrence in implant-based reconstruction: Does the timing matter? Ann Surg Oncol. 2022;30(2):1087-1097 (Dec 10). Doi: 10.1245/s10434-022-12389-0

Key clinical point: Autologous fat grafting (AFG) in the second stage of a 2-stage prosthetic breast reconstruction was linked to a higher risk for breast cancer (BC) recurrence when performed within a year after mastectomy.

Major finding: Patients who did vs did not undergo AFG within 1 year after the primary operation had a significantly increased risk for disease recurrence (hazard ratio 5.701; 95% CI 1.164-27.927). However, delaying the fat grafting beyond 12 months after mastectomy did not affect survival outcomes.

Study details: Findings are from a retrospective cohort study including 267 patients with unilateral invasive BC who underwent total mastectomy and immediate tissue-expander-based reconstruction, of which 203 patients underwent the second-stage operation within 12 months of mastectomy and 64 patients underwent the operation after 12 months of mastectomy.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Lee KT et al. Association of fat graft with breast cancer recurrence in implant-based reconstruction: Does the timing matter? Ann Surg Oncol. 2022;30(2):1087-1097 (Dec 10). Doi: 10.1245/s10434-022-12389-0

Key clinical point: Autologous fat grafting (AFG) in the second stage of a 2-stage prosthetic breast reconstruction was linked to a higher risk for breast cancer (BC) recurrence when performed within a year after mastectomy.

Major finding: Patients who did vs did not undergo AFG within 1 year after the primary operation had a significantly increased risk for disease recurrence (hazard ratio 5.701; 95% CI 1.164-27.927). However, delaying the fat grafting beyond 12 months after mastectomy did not affect survival outcomes.

Study details: Findings are from a retrospective cohort study including 267 patients with unilateral invasive BC who underwent total mastectomy and immediate tissue-expander-based reconstruction, of which 203 patients underwent the second-stage operation within 12 months of mastectomy and 64 patients underwent the operation after 12 months of mastectomy.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Lee KT et al. Association of fat graft with breast cancer recurrence in implant-based reconstruction: Does the timing matter? Ann Surg Oncol. 2022;30(2):1087-1097 (Dec 10). Doi: 10.1245/s10434-022-12389-0

Key clinical point: In patients with early-stage triple-negative breast cancer (TNBC), adding capecitabine to classic anthracycline/taxane-based adjuvant chemotherapy improved overall survival (OS) and carboplatin/paclitaxel was the most effective regimen for improving disease-free survival (DFS).

Major finding: Adjuvant chemotherapy with anthracyclines/taxanes plus capecitabine vs anthracyclines significantly improved OS outcomes (hazard ratio [HR] 0.56; 95% CI 0.36-0.87; probability for ranking the first 29%), whereas carboplatin/paclitaxel vs anthracyclines was the best regimen for improving DFS outcomes (HR 0.51; 95% CI 0.30-0.86; probability for ranking the first 41%).

Study details: Findings are from a network meta-analysis of 27 randomized phase 3 trials that compared adjuvant chemotherapy regimens in patients with resected, stage I-III TNBC.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Petrelli F et al. Adjuvant chemotherapy for resected triple negative breast cancer patients: A network meta-analysis. Breast. 2022;67:8-13 (Dec 15). Doi: 10.1016/j.breast.2022.12.004

Key clinical point: In patients with early-stage triple-negative breast cancer (TNBC), adding capecitabine to classic anthracycline/taxane-based adjuvant chemotherapy improved overall survival (OS) and carboplatin/paclitaxel was the most effective regimen for improving disease-free survival (DFS).

Major finding: Adjuvant chemotherapy with anthracyclines/taxanes plus capecitabine vs anthracyclines significantly improved OS outcomes (hazard ratio [HR] 0.56; 95% CI 0.36-0.87; probability for ranking the first 29%), whereas carboplatin/paclitaxel vs anthracyclines was the best regimen for improving DFS outcomes (HR 0.51; 95% CI 0.30-0.86; probability for ranking the first 41%).

Study details: Findings are from a network meta-analysis of 27 randomized phase 3 trials that compared adjuvant chemotherapy regimens in patients with resected, stage I-III TNBC.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Petrelli F et al. Adjuvant chemotherapy for resected triple negative breast cancer patients: A network meta-analysis. Breast. 2022;67:8-13 (Dec 15). Doi: 10.1016/j.breast.2022.12.004

Key clinical point: In patients with early-stage triple-negative breast cancer (TNBC), adding capecitabine to classic anthracycline/taxane-based adjuvant chemotherapy improved overall survival (OS) and carboplatin/paclitaxel was the most effective regimen for improving disease-free survival (DFS).

Major finding: Adjuvant chemotherapy with anthracyclines/taxanes plus capecitabine vs anthracyclines significantly improved OS outcomes (hazard ratio [HR] 0.56; 95% CI 0.36-0.87; probability for ranking the first 29%), whereas carboplatin/paclitaxel vs anthracyclines was the best regimen for improving DFS outcomes (HR 0.51; 95% CI 0.30-0.86; probability for ranking the first 41%).

Study details: Findings are from a network meta-analysis of 27 randomized phase 3 trials that compared adjuvant chemotherapy regimens in patients with resected, stage I-III TNBC.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Petrelli F et al. Adjuvant chemotherapy for resected triple negative breast cancer patients: A network meta-analysis. Breast. 2022;67:8-13 (Dec 15). Doi: 10.1016/j.breast.2022.12.004

Key clinical point: Treatment with adjuvant chemotherapy significantly improved overall survival (OS) outcomes in patients with estrogen receptor-negative (ER−)/human epidermal growth factor receptor 2-negative (HER2−), T1abN0 breast cancer (BC).

Major finding: After a median follow-up of 7.7 years, a significant improvement was observed in OS with vs without chemotherapy in the overall cohort of patients with T1abN0 BC (hazard ratio 0.35; P  =  .02), along with both subgroups of patients with T1a (log-rank P  =  .001) and T1b (P  =  .001) BC.

Study details: Findings are from a nationwide, retrospective cohort study including 296 patients with ER− /HER2−, T1abN0 BC, of which 79.4% of patients received adjuvant chemotherapy.

Disclosures: This study was supported by the Danish Cancer Society, Denmark, and other sources. Some authors declared receiving personal fees, speaker honorarium, or research grants from various sources.

Source: Hassing CMS et al. Adjuvant chemotherapy in patients with ER-negative/HER2-negative, T1abN0 breast cancer: A nationwide study. Breast Cancer Res Treat. 2022 (Dec 28). Doi: 10.1007/s10549-022-06839-2

Key clinical point: Treatment with adjuvant chemotherapy significantly improved overall survival (OS) outcomes in patients with estrogen receptor-negative (ER−)/human epidermal growth factor receptor 2-negative (HER2−), T1abN0 breast cancer (BC).

Major finding: After a median follow-up of 7.7 years, a significant improvement was observed in OS with vs without chemotherapy in the overall cohort of patients with T1abN0 BC (hazard ratio 0.35; P  =  .02), along with both subgroups of patients with T1a (log-rank P  =  .001) and T1b (P  =  .001) BC.

Study details: Findings are from a nationwide, retrospective cohort study including 296 patients with ER− /HER2−, T1abN0 BC, of which 79.4% of patients received adjuvant chemotherapy.

Disclosures: This study was supported by the Danish Cancer Society, Denmark, and other sources. Some authors declared receiving personal fees, speaker honorarium, or research grants from various sources.

Source: Hassing CMS et al. Adjuvant chemotherapy in patients with ER-negative/HER2-negative, T1abN0 breast cancer: A nationwide study. Breast Cancer Res Treat. 2022 (Dec 28). Doi: 10.1007/s10549-022-06839-2

Key clinical point: Treatment with adjuvant chemotherapy significantly improved overall survival (OS) outcomes in patients with estrogen receptor-negative (ER−)/human epidermal growth factor receptor 2-negative (HER2−), T1abN0 breast cancer (BC).

Major finding: After a median follow-up of 7.7 years, a significant improvement was observed in OS with vs without chemotherapy in the overall cohort of patients with T1abN0 BC (hazard ratio 0.35; P  =  .02), along with both subgroups of patients with T1a (log-rank P  =  .001) and T1b (P  =  .001) BC.

Study details: Findings are from a nationwide, retrospective cohort study including 296 patients with ER− /HER2−, T1abN0 BC, of which 79.4% of patients received adjuvant chemotherapy.

Disclosures: This study was supported by the Danish Cancer Society, Denmark, and other sources. Some authors declared receiving personal fees, speaker honorarium, or research grants from various sources.

Source: Hassing CMS et al. Adjuvant chemotherapy in patients with ER-negative/HER2-negative, T1abN0 breast cancer: A nationwide study. Breast Cancer Res Treat. 2022 (Dec 28). Doi: 10.1007/s10549-022-06839-2

Key clinical point: In patients with advanced human epidermal growth factor receptor 2-positive (HER2+ or ERBB2+) breast cancer (BC) treated with trastuzumab emtansine, the pre-established levels of ERBB2 mRNA expression according to the HER2DX standardized assay served as an important prognostic biomarker in predicting survival outcomes.

Major finding: High, medium, and low levels of ERBB2 mRNA expression were associated with overall response rates of 56%, 29%, and 0%, respectively, with high ERBB2 mRNA expression being associated with both better progression-free survival (P < .001) and overall survival (P  =  .007) outcomes.

Study details: Findings are from a study including 87 patients with HER2+ advanced BC who received treatment with trastuzumab emtansine.

Disclosures: This study was funded by Hospital Clinic, Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche, University of Padova, Italy, and other sources. The authors declared serving as consultants; receiving advisory, lecture, or consulting fees; or having other ties with several sources.

Source: Brasó-Maristany F et al. HER2DX ERBB2 mRNA expression in advanced HER2-positive breast cancer treated with T-DM1. J Natl Cancer Inst. 2022 (Dec 28). Doi: 10.1093/jnci/djac227

Key clinical point: In patients with advanced human epidermal growth factor receptor 2-positive (HER2+ or ERBB2+) breast cancer (BC) treated with trastuzumab emtansine, the pre-established levels of ERBB2 mRNA expression according to the HER2DX standardized assay served as an important prognostic biomarker in predicting survival outcomes.

Major finding: High, medium, and low levels of ERBB2 mRNA expression were associated with overall response rates of 56%, 29%, and 0%, respectively, with high ERBB2 mRNA expression being associated with both better progression-free survival (P < .001) and overall survival (P  =  .007) outcomes.

Study details: Findings are from a study including 87 patients with HER2+ advanced BC who received treatment with trastuzumab emtansine.

Disclosures: This study was funded by Hospital Clinic, Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche, University of Padova, Italy, and other sources. The authors declared serving as consultants; receiving advisory, lecture, or consulting fees; or having other ties with several sources.

Source: Brasó-Maristany F et al. HER2DX ERBB2 mRNA expression in advanced HER2-positive breast cancer treated with T-DM1. J Natl Cancer Inst. 2022 (Dec 28). Doi: 10.1093/jnci/djac227

Key clinical point: In patients with advanced human epidermal growth factor receptor 2-positive (HER2+ or ERBB2+) breast cancer (BC) treated with trastuzumab emtansine, the pre-established levels of ERBB2 mRNA expression according to the HER2DX standardized assay served as an important prognostic biomarker in predicting survival outcomes.

Major finding: High, medium, and low levels of ERBB2 mRNA expression were associated with overall response rates of 56%, 29%, and 0%, respectively, with high ERBB2 mRNA expression being associated with both better progression-free survival (P < .001) and overall survival (P  =  .007) outcomes.

Study details: Findings are from a study including 87 patients with HER2+ advanced BC who received treatment with trastuzumab emtansine.

Disclosures: This study was funded by Hospital Clinic, Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche, University of Padova, Italy, and other sources. The authors declared serving as consultants; receiving advisory, lecture, or consulting fees; or having other ties with several sources.

Source: Brasó-Maristany F et al. HER2DX ERBB2 mRNA expression in advanced HER2-positive breast cancer treated with T-DM1. J Natl Cancer Inst. 2022 (Dec 28). Doi: 10.1093/jnci/djac227

Key clinical point: Addition of atezolizumab to carboplatin+paclitaxel in the neoadjuvant setting improved the pathological complete response (pCR) rate in patients with stage II-III triple-negative breast cancer (TNBC).

Major finding: After a median follow-up of 6.6 months, a significantly higher proportion of patients achieved pCR in the atezolizumab+chemotherapy vs chemotherapy-only group (55.6% vs 18.8%; P  =  .018). However, the increase in the percentage of tumor infiltrating lymphocytes was nominal and not significantly different between both groups (P  =  .36). Grade ≥3 treatment-related adverse events were reported by 62.5% vs 57.8% of patients in the only chemotherapy vs atezolizumab+chemotherapy group, respectively.

Study details: Findings are from the phase 2 NCI-10013 study including 67 patients with previously untreated stage II and III TNBC who were randomly assigned to receive neoadjuvant carboplatin+paclitaxel with or without atezolizumab.

Disclosures: This study was supported by the US National Cancer Institute Cancer Therapy Evaluation Program. Some authors declared receiving research grants or having other financial or non-financial ties with several sources.

Source: Ademuyiwa FO et al. A randomized phase 2 study of neoadjuvant carboplatin and paclitaxel with or without atezolizumab in triple negative breast cancer (TNBC) - NCI 10013. NPJ Breast Cancer. 2022;8(1):134 (Dec 30). Doi: 10.1038/s41523-022-00500-3

Key clinical point: Addition of atezolizumab to carboplatin+paclitaxel in the neoadjuvant setting improved the pathological complete response (pCR) rate in patients with stage II-III triple-negative breast cancer (TNBC).

Major finding: After a median follow-up of 6.6 months, a significantly higher proportion of patients achieved pCR in the atezolizumab+chemotherapy vs chemotherapy-only group (55.6% vs 18.8%; P  =  .018). However, the increase in the percentage of tumor infiltrating lymphocytes was nominal and not significantly different between both groups (P  =  .36). Grade ≥3 treatment-related adverse events were reported by 62.5% vs 57.8% of patients in the only chemotherapy vs atezolizumab+chemotherapy group, respectively.

Study details: Findings are from the phase 2 NCI-10013 study including 67 patients with previously untreated stage II and III TNBC who were randomly assigned to receive neoadjuvant carboplatin+paclitaxel with or without atezolizumab.

Disclosures: This study was supported by the US National Cancer Institute Cancer Therapy Evaluation Program. Some authors declared receiving research grants or having other financial or non-financial ties with several sources.

Source: Ademuyiwa FO et al. A randomized phase 2 study of neoadjuvant carboplatin and paclitaxel with or without atezolizumab in triple negative breast cancer (TNBC) - NCI 10013. NPJ Breast Cancer. 2022;8(1):134 (Dec 30). Doi: 10.1038/s41523-022-00500-3

Key clinical point: Addition of atezolizumab to carboplatin+paclitaxel in the neoadjuvant setting improved the pathological complete response (pCR) rate in patients with stage II-III triple-negative breast cancer (TNBC).

Major finding: After a median follow-up of 6.6 months, a significantly higher proportion of patients achieved pCR in the atezolizumab+chemotherapy vs chemotherapy-only group (55.6% vs 18.8%; P  =  .018). However, the increase in the percentage of tumor infiltrating lymphocytes was nominal and not significantly different between both groups (P  =  .36). Grade ≥3 treatment-related adverse events were reported by 62.5% vs 57.8% of patients in the only chemotherapy vs atezolizumab+chemotherapy group, respectively.

Study details: Findings are from the phase 2 NCI-10013 study including 67 patients with previously untreated stage II and III TNBC who were randomly assigned to receive neoadjuvant carboplatin+paclitaxel with or without atezolizumab.

Disclosures: This study was supported by the US National Cancer Institute Cancer Therapy Evaluation Program. Some authors declared receiving research grants or having other financial or non-financial ties with several sources.

Source: Ademuyiwa FO et al. A randomized phase 2 study of neoadjuvant carboplatin and paclitaxel with or without atezolizumab in triple negative breast cancer (TNBC) - NCI 10013. NPJ Breast Cancer. 2022;8(1):134 (Dec 30). Doi: 10.1038/s41523-022-00500-3