Article

Women who conceived within 6 months of having a miscarriage or an induced abortion did not appear to be at an increased risk of a problematic pregnancy, a new study of more than 70,000 live births in Norway has found.

The findings, published online in PLOS Medicine, should help women and clinicians navigate conflicting guidance over how soon it is safe to conceive again after a pregnancy loss, said Gizachew Tessema, PhD, senior research fellow at Curtin University, Perth, Australia, and the lead author of the research.

“Especially after a miscarriage, women want to conceive again,” Dr. Tessema told this news organization. “Why should they wait if there’s no increased risk?”

On the international front, the World Health Organization advises patients not to attempt to become pregnant until a minimum of 6 months after an abortion or miscarriage. Those 2007 recommendations spurred Dr. Tessema and his colleagues to take a deeper dive into risk factors associated with pregnancies following a shorter interval. 

Two-thirds of women in the study conceived again within 6 months of having a miscarriage. Only a quarter of women who had an induced abortion were pregnant again within that same timeframe.

Using Norway’s national health registries, the researchers examined the outcomes of 49,058 births following a miscarriage and 23,707 births after an induced abortion between 2008 and 2016. The birth registry includes information on livebirths, stillbirths, miscarriages, and induced abortions, with detailed descriptions provided around how a miscarriage or abortion is identified. The study included only miscarriages reported through the health care system.

Expanding on other studies that have shown no adverse outcomes with those pregnancy intervals, Dr. Tessema and colleagues found that women who became pregnant shortly after a miscarriage or abortion were not at a higher risk for delivering preterm, having newborns that were small for gestational age (SGA) or large for gestational age (LGA), or developing preeclampsia or gestational diabetes.

Dr. Tessema and his colleagues found a slightly smaller percentage of women who conceived within 3 months, compared with those who became pregnant within 6-11 months after a miscarriage (8.6% to 10.1%). Women who conceived within 3 months of an induced abortion had a slightly, but statistically nonsignificant (P = .07), increased risk for SGA, compared with those who conceived between 6 and 11 months (11.5% to 10%).

No greater risk was shown for the other adverse outcomes – preterm births, LGA, preeclampsia, and GDM – for women who became pregnant within 6 months of an abortion or miscarriage.

The results should reassure women who want to get pregnant again soon after abortions or miscarriage, according to Scott Sullivan, MD, the director of high-risk ob.gyn. at Inova Health, Fairfax, Va.

Often, patients hear conflicting advice from doctors, friends, or medical associations about the best time to try for a baby following a miscarriage or abortion, in part because there are differences in various guidelines. Adding to the confusion is a lack of robust research and data on pregnancy loss, especially in the United States, he said.

“The entire topic of pregnancy loss is underappreciated by the public at large – how painful this is for people, how common it is,” Dr. Sullivan said in an interview. “We need research and resources on it. It’s not even tracked routinely in the United States like it is in other countries.”

Dr. Sullivan said he typically tells patients they can try to get pregnant again right away, following recommendations from the American College of Obstetricians and Gynecologists, which say that patients can conceive as quickly as 2 weeks after an early pregnancy loss.

But he cautions that not all patients are mentally ready to make another attempt that soon, especially if they are still grieving their pregnancy loss.

“Even if you’re physically ready, a lot of people are not emotionally ready, because there’s a grieving process,” Dr. Sullivan said. “That’s very different for people.”
 

The WHO’s guidelines for developed countries

The WHO developed its guidelines based on research from lower income countries, including one study across Latin America that concluded pregnancy outcomes were worse for women who waited less than 6 months to conceive following an abortion or miscarriage.

Dr. Tessema noted his research is limited because it focused on Norway, a high-income country where women have guaranteed access to health care. Outcomes may be worse in developing countries where incomes are lower and health care inequality is greater, he said.

“The issue is when this international guideline was developed, most of the evidence is from low- and middle-income countries,” Dr. Tessema said. “No studies were conducted from high income cities. We said: ‘This is a different context.’ These recommendations may not be appropriate for this setting.”

The study was supported with funding by the Research Council of Norway through its Centres of Excellence funding program, the National Health and Medical Research Council, the Raine Medical Research Foundation, and the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme. None of the authors report relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women who conceived within 6 months of having a miscarriage or an induced abortion did not appear to be at an increased risk of a problematic pregnancy, a new study of more than 70,000 live births in Norway has found.

The findings, published online in PLOS Medicine, should help women and clinicians navigate conflicting guidance over how soon it is safe to conceive again after a pregnancy loss, said Gizachew Tessema, PhD, senior research fellow at Curtin University, Perth, Australia, and the lead author of the research.

“Especially after a miscarriage, women want to conceive again,” Dr. Tessema told this news organization. “Why should they wait if there’s no increased risk?”

On the international front, the World Health Organization advises patients not to attempt to become pregnant until a minimum of 6 months after an abortion or miscarriage. Those 2007 recommendations spurred Dr. Tessema and his colleagues to take a deeper dive into risk factors associated with pregnancies following a shorter interval. 

Two-thirds of women in the study conceived again within 6 months of having a miscarriage. Only a quarter of women who had an induced abortion were pregnant again within that same timeframe.

Using Norway’s national health registries, the researchers examined the outcomes of 49,058 births following a miscarriage and 23,707 births after an induced abortion between 2008 and 2016. The birth registry includes information on livebirths, stillbirths, miscarriages, and induced abortions, with detailed descriptions provided around how a miscarriage or abortion is identified. The study included only miscarriages reported through the health care system.

Expanding on other studies that have shown no adverse outcomes with those pregnancy intervals, Dr. Tessema and colleagues found that women who became pregnant shortly after a miscarriage or abortion were not at a higher risk for delivering preterm, having newborns that were small for gestational age (SGA) or large for gestational age (LGA), or developing preeclampsia or gestational diabetes.

Dr. Tessema and his colleagues found a slightly smaller percentage of women who conceived within 3 months, compared with those who became pregnant within 6-11 months after a miscarriage (8.6% to 10.1%). Women who conceived within 3 months of an induced abortion had a slightly, but statistically nonsignificant (P = .07), increased risk for SGA, compared with those who conceived between 6 and 11 months (11.5% to 10%).

No greater risk was shown for the other adverse outcomes – preterm births, LGA, preeclampsia, and GDM – for women who became pregnant within 6 months of an abortion or miscarriage.

The results should reassure women who want to get pregnant again soon after abortions or miscarriage, according to Scott Sullivan, MD, the director of high-risk ob.gyn. at Inova Health, Fairfax, Va.

Often, patients hear conflicting advice from doctors, friends, or medical associations about the best time to try for a baby following a miscarriage or abortion, in part because there are differences in various guidelines. Adding to the confusion is a lack of robust research and data on pregnancy loss, especially in the United States, he said.

“The entire topic of pregnancy loss is underappreciated by the public at large – how painful this is for people, how common it is,” Dr. Sullivan said in an interview. “We need research and resources on it. It’s not even tracked routinely in the United States like it is in other countries.”

Dr. Sullivan said he typically tells patients they can try to get pregnant again right away, following recommendations from the American College of Obstetricians and Gynecologists, which say that patients can conceive as quickly as 2 weeks after an early pregnancy loss.

But he cautions that not all patients are mentally ready to make another attempt that soon, especially if they are still grieving their pregnancy loss.

“Even if you’re physically ready, a lot of people are not emotionally ready, because there’s a grieving process,” Dr. Sullivan said. “That’s very different for people.”
 

The WHO’s guidelines for developed countries

The WHO developed its guidelines based on research from lower income countries, including one study across Latin America that concluded pregnancy outcomes were worse for women who waited less than 6 months to conceive following an abortion or miscarriage.

Dr. Tessema noted his research is limited because it focused on Norway, a high-income country where women have guaranteed access to health care. Outcomes may be worse in developing countries where incomes are lower and health care inequality is greater, he said.

“The issue is when this international guideline was developed, most of the evidence is from low- and middle-income countries,” Dr. Tessema said. “No studies were conducted from high income cities. We said: ‘This is a different context.’ These recommendations may not be appropriate for this setting.”

The study was supported with funding by the Research Council of Norway through its Centres of Excellence funding program, the National Health and Medical Research Council, the Raine Medical Research Foundation, and the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme. None of the authors report relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women who conceived within 6 months of having a miscarriage or an induced abortion did not appear to be at an increased risk of a problematic pregnancy, a new study of more than 70,000 live births in Norway has found.

The findings, published online in PLOS Medicine, should help women and clinicians navigate conflicting guidance over how soon it is safe to conceive again after a pregnancy loss, said Gizachew Tessema, PhD, senior research fellow at Curtin University, Perth, Australia, and the lead author of the research.

“Especially after a miscarriage, women want to conceive again,” Dr. Tessema told this news organization. “Why should they wait if there’s no increased risk?”

On the international front, the World Health Organization advises patients not to attempt to become pregnant until a minimum of 6 months after an abortion or miscarriage. Those 2007 recommendations spurred Dr. Tessema and his colleagues to take a deeper dive into risk factors associated with pregnancies following a shorter interval. 

Two-thirds of women in the study conceived again within 6 months of having a miscarriage. Only a quarter of women who had an induced abortion were pregnant again within that same timeframe.

Using Norway’s national health registries, the researchers examined the outcomes of 49,058 births following a miscarriage and 23,707 births after an induced abortion between 2008 and 2016. The birth registry includes information on livebirths, stillbirths, miscarriages, and induced abortions, with detailed descriptions provided around how a miscarriage or abortion is identified. The study included only miscarriages reported through the health care system.

Expanding on other studies that have shown no adverse outcomes with those pregnancy intervals, Dr. Tessema and colleagues found that women who became pregnant shortly after a miscarriage or abortion were not at a higher risk for delivering preterm, having newborns that were small for gestational age (SGA) or large for gestational age (LGA), or developing preeclampsia or gestational diabetes.

Dr. Tessema and his colleagues found a slightly smaller percentage of women who conceived within 3 months, compared with those who became pregnant within 6-11 months after a miscarriage (8.6% to 10.1%). Women who conceived within 3 months of an induced abortion had a slightly, but statistically nonsignificant (P = .07), increased risk for SGA, compared with those who conceived between 6 and 11 months (11.5% to 10%).

No greater risk was shown for the other adverse outcomes – preterm births, LGA, preeclampsia, and GDM – for women who became pregnant within 6 months of an abortion or miscarriage.

The results should reassure women who want to get pregnant again soon after abortions or miscarriage, according to Scott Sullivan, MD, the director of high-risk ob.gyn. at Inova Health, Fairfax, Va.

Often, patients hear conflicting advice from doctors, friends, or medical associations about the best time to try for a baby following a miscarriage or abortion, in part because there are differences in various guidelines. Adding to the confusion is a lack of robust research and data on pregnancy loss, especially in the United States, he said.

“The entire topic of pregnancy loss is underappreciated by the public at large – how painful this is for people, how common it is,” Dr. Sullivan said in an interview. “We need research and resources on it. It’s not even tracked routinely in the United States like it is in other countries.”

Dr. Sullivan said he typically tells patients they can try to get pregnant again right away, following recommendations from the American College of Obstetricians and Gynecologists, which say that patients can conceive as quickly as 2 weeks after an early pregnancy loss.

But he cautions that not all patients are mentally ready to make another attempt that soon, especially if they are still grieving their pregnancy loss.

“Even if you’re physically ready, a lot of people are not emotionally ready, because there’s a grieving process,” Dr. Sullivan said. “That’s very different for people.”
 

The WHO’s guidelines for developed countries

The WHO developed its guidelines based on research from lower income countries, including one study across Latin America that concluded pregnancy outcomes were worse for women who waited less than 6 months to conceive following an abortion or miscarriage.

Dr. Tessema noted his research is limited because it focused on Norway, a high-income country where women have guaranteed access to health care. Outcomes may be worse in developing countries where incomes are lower and health care inequality is greater, he said.

“The issue is when this international guideline was developed, most of the evidence is from low- and middle-income countries,” Dr. Tessema said. “No studies were conducted from high income cities. We said: ‘This is a different context.’ These recommendations may not be appropriate for this setting.”

The study was supported with funding by the Research Council of Norway through its Centres of Excellence funding program, the National Health and Medical Research Council, the Raine Medical Research Foundation, and the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme. None of the authors report relevant financial relationships.

A version of this article first appeared on Medscape.com.

Several studies have addressed the efficacy of COVID vaccines in patients with autoimmune and rheumatic diseases owing to the concern for possible reduced vaccine immunogenicity in patients who are immunocompromised or taking immunosuppressive medications. With the availability of additional booster doses for the COVID vaccines, the effect of immunosuppressive medications on the humoral response to mRNA vaccines has been of increased interest in terms of counseling patients on how to manage their medications and vaccine timing. Prior studies have suggested that holding methotrexate after COVID vaccine administration improves antibody response to the COVID vaccine. Stahl and colleagues performed a retrospective study to look at vaccine response to a third (booster) dose in patients with rheumatoid arthritis (RA) over 65 years of age (vs those under 65 years of age) and found that patients over 65 receiving methotrexate had lower levels of neutralizing antibodies than did those receiving other treatments for RA, whereas no differences were seen with different treatments among patients under 65. Although COVID vaccine guidance continues to evolve, this finding raises the possibility of a need to tailor guidance in older patients with RA. However, the finding is far from conclusive given the small number of patients in the study.

In addition to COVID vaccine efficacy, the possibility of vaccine-related adverse effects has been a topic of concern in the rheumatology community, especially regarding the potential for a flare of autoimmune diseases. Anxiety regarding adverse effects may also exacerbate COVID vaccine hesitancy among some people. Naveen and colleagues performed an online international cross-sectional survey study regarding rheumatic diseases and 7-day adverse events. Over 9000 people completed the survey, about half of whom had autoimmune diseases (including nonrheumatic autoimmune diseases). Roughly three quarters of patients with RA reported adverse effects, with differences seen in frequencies of events between the different vaccine manufacturers. However, the majority of these adverse effects were minor (such as fatigue, headache, and body ache), without substantial differences between those with inactive and those with active RA.

The treat-to-target strategy is well-accepted in treatment of RA and pursuit of improved long-term disease outcomes. Hartman and colleagues evaluated the effect of using a treat-to-target strategy starting with the combination therapy with RA-light (COBRA-light) protocol (with initial methotrexate and tapering prednisolone) in early RA. Patients who were deemed at high risk for worsening RA (n = 150) received COBRA-light, whereas those in the low-risk category (n = 40) received methotrexate monotherapy. At 13 weeks, nonresponders were randomized to intensification or continuation of their regimens, with a primary endpoint of European Alliance of Associations for Rheumatology (EULAR) response and secondary endpoint of Disease Activity Score (DAS44). After 13 weeks, 73% of patients in the high-risk category achieved the targets of EULAR good response and DAS44 < 1.6, whereas after 26 weeks, 80% of patients who received intensified therapy and 44% of those who continued their regimens reached the target, though these numbers were small. Overall, the strategy appears to be successful in treatment of early RA in patients at high risk for disease progression, but it does lead to increased use of higher chronic glucocorticoid doses. In addition, the small numbers of patients in the low-risk category, as well as their less aggressive treatment, does not allow for a nuanced analysis of the best initial treatment in this group of patients.

Finally, a cohort study by Takanashi and colleagues evaluated the rates of seropositivity for rheumatoid factor (RF) and anti–cyclic citrullinated peptide (anti-CCP) in patients diagnosed with RA and its association with demographic categories. Seropositivity was associated with smoking and family history of RA, as expected. Among the 1685 patients, 83% of whom were women, older age at RA diagnosis was associated with seronegativity for RF and CCP in women but not in men. The decline in seropositivity with age among women cannot be further evaluated with the limited information in this small study and may have to do with other factors, including erosive or inflammatory osteoarthritis.

Several studies have addressed the efficacy of COVID vaccines in patients with autoimmune and rheumatic diseases owing to the concern for possible reduced vaccine immunogenicity in patients who are immunocompromised or taking immunosuppressive medications. With the availability of additional booster doses for the COVID vaccines, the effect of immunosuppressive medications on the humoral response to mRNA vaccines has been of increased interest in terms of counseling patients on how to manage their medications and vaccine timing. Prior studies have suggested that holding methotrexate after COVID vaccine administration improves antibody response to the COVID vaccine. Stahl and colleagues performed a retrospective study to look at vaccine response to a third (booster) dose in patients with rheumatoid arthritis (RA) over 65 years of age (vs those under 65 years of age) and found that patients over 65 receiving methotrexate had lower levels of neutralizing antibodies than did those receiving other treatments for RA, whereas no differences were seen with different treatments among patients under 65. Although COVID vaccine guidance continues to evolve, this finding raises the possibility of a need to tailor guidance in older patients with RA. However, the finding is far from conclusive given the small number of patients in the study.

In addition to COVID vaccine efficacy, the possibility of vaccine-related adverse effects has been a topic of concern in the rheumatology community, especially regarding the potential for a flare of autoimmune diseases. Anxiety regarding adverse effects may also exacerbate COVID vaccine hesitancy among some people. Naveen and colleagues performed an online international cross-sectional survey study regarding rheumatic diseases and 7-day adverse events. Over 9000 people completed the survey, about half of whom had autoimmune diseases (including nonrheumatic autoimmune diseases). Roughly three quarters of patients with RA reported adverse effects, with differences seen in frequencies of events between the different vaccine manufacturers. However, the majority of these adverse effects were minor (such as fatigue, headache, and body ache), without substantial differences between those with inactive and those with active RA.

The treat-to-target strategy is well-accepted in treatment of RA and pursuit of improved long-term disease outcomes. Hartman and colleagues evaluated the effect of using a treat-to-target strategy starting with the combination therapy with RA-light (COBRA-light) protocol (with initial methotrexate and tapering prednisolone) in early RA. Patients who were deemed at high risk for worsening RA (n = 150) received COBRA-light, whereas those in the low-risk category (n = 40) received methotrexate monotherapy. At 13 weeks, nonresponders were randomized to intensification or continuation of their regimens, with a primary endpoint of European Alliance of Associations for Rheumatology (EULAR) response and secondary endpoint of Disease Activity Score (DAS44). After 13 weeks, 73% of patients in the high-risk category achieved the targets of EULAR good response and DAS44 < 1.6, whereas after 26 weeks, 80% of patients who received intensified therapy and 44% of those who continued their regimens reached the target, though these numbers were small. Overall, the strategy appears to be successful in treatment of early RA in patients at high risk for disease progression, but it does lead to increased use of higher chronic glucocorticoid doses. In addition, the small numbers of patients in the low-risk category, as well as their less aggressive treatment, does not allow for a nuanced analysis of the best initial treatment in this group of patients.

Finally, a cohort study by Takanashi and colleagues evaluated the rates of seropositivity for rheumatoid factor (RF) and anti–cyclic citrullinated peptide (anti-CCP) in patients diagnosed with RA and its association with demographic categories. Seropositivity was associated with smoking and family history of RA, as expected. Among the 1685 patients, 83% of whom were women, older age at RA diagnosis was associated with seronegativity for RF and CCP in women but not in men. The decline in seropositivity with age among women cannot be further evaluated with the limited information in this small study and may have to do with other factors, including erosive or inflammatory osteoarthritis.

Several studies have addressed the efficacy of COVID vaccines in patients with autoimmune and rheumatic diseases owing to the concern for possible reduced vaccine immunogenicity in patients who are immunocompromised or taking immunosuppressive medications. With the availability of additional booster doses for the COVID vaccines, the effect of immunosuppressive medications on the humoral response to mRNA vaccines has been of increased interest in terms of counseling patients on how to manage their medications and vaccine timing. Prior studies have suggested that holding methotrexate after COVID vaccine administration improves antibody response to the COVID vaccine. Stahl and colleagues performed a retrospective study to look at vaccine response to a third (booster) dose in patients with rheumatoid arthritis (RA) over 65 years of age (vs those under 65 years of age) and found that patients over 65 receiving methotrexate had lower levels of neutralizing antibodies than did those receiving other treatments for RA, whereas no differences were seen with different treatments among patients under 65. Although COVID vaccine guidance continues to evolve, this finding raises the possibility of a need to tailor guidance in older patients with RA. However, the finding is far from conclusive given the small number of patients in the study.

In addition to COVID vaccine efficacy, the possibility of vaccine-related adverse effects has been a topic of concern in the rheumatology community, especially regarding the potential for a flare of autoimmune diseases. Anxiety regarding adverse effects may also exacerbate COVID vaccine hesitancy among some people. Naveen and colleagues performed an online international cross-sectional survey study regarding rheumatic diseases and 7-day adverse events. Over 9000 people completed the survey, about half of whom had autoimmune diseases (including nonrheumatic autoimmune diseases). Roughly three quarters of patients with RA reported adverse effects, with differences seen in frequencies of events between the different vaccine manufacturers. However, the majority of these adverse effects were minor (such as fatigue, headache, and body ache), without substantial differences between those with inactive and those with active RA.

The treat-to-target strategy is well-accepted in treatment of RA and pursuit of improved long-term disease outcomes. Hartman and colleagues evaluated the effect of using a treat-to-target strategy starting with the combination therapy with RA-light (COBRA-light) protocol (with initial methotrexate and tapering prednisolone) in early RA. Patients who were deemed at high risk for worsening RA (n = 150) received COBRA-light, whereas those in the low-risk category (n = 40) received methotrexate monotherapy. At 13 weeks, nonresponders were randomized to intensification or continuation of their regimens, with a primary endpoint of European Alliance of Associations for Rheumatology (EULAR) response and secondary endpoint of Disease Activity Score (DAS44). After 13 weeks, 73% of patients in the high-risk category achieved the targets of EULAR good response and DAS44 < 1.6, whereas after 26 weeks, 80% of patients who received intensified therapy and 44% of those who continued their regimens reached the target, though these numbers were small. Overall, the strategy appears to be successful in treatment of early RA in patients at high risk for disease progression, but it does lead to increased use of higher chronic glucocorticoid doses. In addition, the small numbers of patients in the low-risk category, as well as their less aggressive treatment, does not allow for a nuanced analysis of the best initial treatment in this group of patients.

Finally, a cohort study by Takanashi and colleagues evaluated the rates of seropositivity for rheumatoid factor (RF) and anti–cyclic citrullinated peptide (anti-CCP) in patients diagnosed with RA and its association with demographic categories. Seropositivity was associated with smoking and family history of RA, as expected. Among the 1685 patients, 83% of whom were women, older age at RA diagnosis was associated with seronegativity for RF and CCP in women but not in men. The decline in seropositivity with age among women cannot be further evaluated with the limited information in this small study and may have to do with other factors, including erosive or inflammatory osteoarthritis.

A study by Hofheinz and colleagues evaluated whether targeting the human epidermal growth factor receptor 2 (HER2) pathway can improve outcomes in early-stage esophagogastric adenocarcinoma (EGA).¹ About 15%-20% of EGA overexpress HER2. In the metastatic setting, anti-HER2 therapies have an established role. Trastuzumab in combination with chemotherapy has been part of standard treatment for these tumors for over a decade and now immunotherapy, based on the ongoing KEYNOTE-811 study, has been proven effective as well.^2,3 However, prior attempts to effectively target HER2 in the early stage have not been successful.⁴

A phase 2 trial conducted by the AIO EGA Study Group evaluated the addition of trastuzumab and pertuzumab to FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) chemotherapy in resectable HER2-positive EGA. The trial closed early, before planned full accrual, when the results of the JACOB trial, which evaluated the addition of pertuzumab in the metastatic setting, came out as negative.⁵ However, the results are still worth discussing here. A total of 81 patients were enrolled in this study (40 in the experimental arm and 41 in the chemotherapy-only control arm). Pathologic complete response was significantly improved with the addition of anti-HER2 therapy (35% vs 12%; P = .02). The rates of R0 resection and surgical complications were similar. Median disease-free survival was not reached in the experimental arm (26 months in the control arm). This study suggests that evaluation of anti-HER2 agents in combination with chemotherapy is warranted. Given the promising results of the KEYNOTE-811 study, future studies should consider incorporative immunotherapy as well.

The Neo-PLANET phase 2 study by Tang and colleagues evaluated the addition of camrelizumab (anti-PD1 antibody) to concurrent chemoradiation in the treatment of advanced EGA.⁶ The 36 patients enrolled in this study received induction chemotherapy with capecitabine and oxaliplatin followed by chemoradiation with the same chemotherapy backbone. Camrelizumab was added from the time of all chemotherapy initiation. The pathologic complete response observed (33.3%) compared favorably to historical references. No new safety signals were identified. Current standards for resectable EGA include adjuvant nivolumab in patients who have residual disease at the time of resection post chemoradiation. This study demonstrated that the addition of immunotherapy earlier in the treatment course is safe and possibly efficacious. The prospective randomized phase 2/3 ECOG-ACRIN 2174 study will evaluate the addition of nivolumab to chemoradiation, as well as the addition of ipilimumab to nivolumab in the adjuvant setting, and will answer the question regarding the benefits of immunotherapy used earlier in the course of disease in a prospective randomized manner (NCT03604991).

The study by de Jongh and colleagues evaluated the pattern of lymph node metastasis after neoadjuvant chemotherapy with relation to the location of the primary gastric tumor. Tumors from 212 patients who were previously enrolled in the Dutch LOGICA trial comparing laparoscopy vs open D2 gastrectomy were included in this analysis. Although the primary tumor location (proximal vs distal) was associated with a higher frequency of metastasis to certain lymph node groups, this relationship was not exclusive. As such, the extent of lymphadenectomy should not depend on the primary location of the tumor and is not affected by neoadjuvant chemotherapy.

Additional References

1. Hofheinz R-D, Merx K, Haag GM, et al. FLOT versus FLOT/trastuzumab/pertuzumab perioperative therapy of human epidermal growth factor receptor 2–positive resectable esophagogastric adenocarcinoma: A randomized phase II trial of the AIO EGA Study Group. J Clin Oncol. 2022;40:3750-3761. Doi: 10.1200/JCO.22.00380

2. Janjigian YY, Kawazoe A, Yañez P, et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021;600:727-730. Doi: 10.1038/s41586-021-04161-3

3. Bang Y-J, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687-697. Doi: 10.1016/S0140-6736(10)61121-X

4. Safran HP, Winter K, Hilson D, et al. Trastuzumab with trimodality treatment for oesophageal adenocarcinoma with HER2 overexpression (NRG Oncology/RTOG 1010): A multicentre, randomised, phase 3 trial. Lancet Oncol. 2022;23:259-269. Doi: 10.1016/S1470-2045(21)00718-X

5. Tabernero J, Hoff PM, Shen L, et al. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): Final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018:19:1372-1384. Doi: 10.1016/S1470-2045(18)30481-9

6. Tang Z, Wang Y, Liu D, et al. The Neo-PLANET phase II trial of neoadjuvant camrelizumab plus concurrent chemoradiotherapy in locally advanced adenocarcinoma of stomach or gastroesophageal junction. Nat Commun 2022;13:6807. Doi: 10.1038/s41467-022-34403-5

A study by Hofheinz and colleagues evaluated whether targeting the human epidermal growth factor receptor 2 (HER2) pathway can improve outcomes in early-stage esophagogastric adenocarcinoma (EGA).¹ About 15%-20% of EGA overexpress HER2. In the metastatic setting, anti-HER2 therapies have an established role. Trastuzumab in combination with chemotherapy has been part of standard treatment for these tumors for over a decade and now immunotherapy, based on the ongoing KEYNOTE-811 study, has been proven effective as well.^2,3 However, prior attempts to effectively target HER2 in the early stage have not been successful.⁴

A phase 2 trial conducted by the AIO EGA Study Group evaluated the addition of trastuzumab and pertuzumab to FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) chemotherapy in resectable HER2-positive EGA. The trial closed early, before planned full accrual, when the results of the JACOB trial, which evaluated the addition of pertuzumab in the metastatic setting, came out as negative.⁵ However, the results are still worth discussing here. A total of 81 patients were enrolled in this study (40 in the experimental arm and 41 in the chemotherapy-only control arm). Pathologic complete response was significantly improved with the addition of anti-HER2 therapy (35% vs 12%; P = .02). The rates of R0 resection and surgical complications were similar. Median disease-free survival was not reached in the experimental arm (26 months in the control arm). This study suggests that evaluation of anti-HER2 agents in combination with chemotherapy is warranted. Given the promising results of the KEYNOTE-811 study, future studies should consider incorporative immunotherapy as well.

The Neo-PLANET phase 2 study by Tang and colleagues evaluated the addition of camrelizumab (anti-PD1 antibody) to concurrent chemoradiation in the treatment of advanced EGA.⁶ The 36 patients enrolled in this study received induction chemotherapy with capecitabine and oxaliplatin followed by chemoradiation with the same chemotherapy backbone. Camrelizumab was added from the time of all chemotherapy initiation. The pathologic complete response observed (33.3%) compared favorably to historical references. No new safety signals were identified. Current standards for resectable EGA include adjuvant nivolumab in patients who have residual disease at the time of resection post chemoradiation. This study demonstrated that the addition of immunotherapy earlier in the treatment course is safe and possibly efficacious. The prospective randomized phase 2/3 ECOG-ACRIN 2174 study will evaluate the addition of nivolumab to chemoradiation, as well as the addition of ipilimumab to nivolumab in the adjuvant setting, and will answer the question regarding the benefits of immunotherapy used earlier in the course of disease in a prospective randomized manner (NCT03604991).

The study by de Jongh and colleagues evaluated the pattern of lymph node metastasis after neoadjuvant chemotherapy with relation to the location of the primary gastric tumor. Tumors from 212 patients who were previously enrolled in the Dutch LOGICA trial comparing laparoscopy vs open D2 gastrectomy were included in this analysis. Although the primary tumor location (proximal vs distal) was associated with a higher frequency of metastasis to certain lymph node groups, this relationship was not exclusive. As such, the extent of lymphadenectomy should not depend on the primary location of the tumor and is not affected by neoadjuvant chemotherapy.

Additional References

1. Hofheinz R-D, Merx K, Haag GM, et al. FLOT versus FLOT/trastuzumab/pertuzumab perioperative therapy of human epidermal growth factor receptor 2–positive resectable esophagogastric adenocarcinoma: A randomized phase II trial of the AIO EGA Study Group. J Clin Oncol. 2022;40:3750-3761. Doi: 10.1200/JCO.22.00380

2. Janjigian YY, Kawazoe A, Yañez P, et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021;600:727-730. Doi: 10.1038/s41586-021-04161-3

3. Bang Y-J, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687-697. Doi: 10.1016/S0140-6736(10)61121-X

4. Safran HP, Winter K, Hilson D, et al. Trastuzumab with trimodality treatment for oesophageal adenocarcinoma with HER2 overexpression (NRG Oncology/RTOG 1010): A multicentre, randomised, phase 3 trial. Lancet Oncol. 2022;23:259-269. Doi: 10.1016/S1470-2045(21)00718-X

5. Tabernero J, Hoff PM, Shen L, et al. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): Final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018:19:1372-1384. Doi: 10.1016/S1470-2045(18)30481-9

6. Tang Z, Wang Y, Liu D, et al. The Neo-PLANET phase II trial of neoadjuvant camrelizumab plus concurrent chemoradiotherapy in locally advanced adenocarcinoma of stomach or gastroesophageal junction. Nat Commun 2022;13:6807. Doi: 10.1038/s41467-022-34403-5

A study by Hofheinz and colleagues evaluated whether targeting the human epidermal growth factor receptor 2 (HER2) pathway can improve outcomes in early-stage esophagogastric adenocarcinoma (EGA).¹ About 15%-20% of EGA overexpress HER2. In the metastatic setting, anti-HER2 therapies have an established role. Trastuzumab in combination with chemotherapy has been part of standard treatment for these tumors for over a decade and now immunotherapy, based on the ongoing KEYNOTE-811 study, has been proven effective as well.^2,3 However, prior attempts to effectively target HER2 in the early stage have not been successful.⁴

A phase 2 trial conducted by the AIO EGA Study Group evaluated the addition of trastuzumab and pertuzumab to FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) chemotherapy in resectable HER2-positive EGA. The trial closed early, before planned full accrual, when the results of the JACOB trial, which evaluated the addition of pertuzumab in the metastatic setting, came out as negative.⁵ However, the results are still worth discussing here. A total of 81 patients were enrolled in this study (40 in the experimental arm and 41 in the chemotherapy-only control arm). Pathologic complete response was significantly improved with the addition of anti-HER2 therapy (35% vs 12%; P = .02). The rates of R0 resection and surgical complications were similar. Median disease-free survival was not reached in the experimental arm (26 months in the control arm). This study suggests that evaluation of anti-HER2 agents in combination with chemotherapy is warranted. Given the promising results of the KEYNOTE-811 study, future studies should consider incorporative immunotherapy as well.

The Neo-PLANET phase 2 study by Tang and colleagues evaluated the addition of camrelizumab (anti-PD1 antibody) to concurrent chemoradiation in the treatment of advanced EGA.⁶ The 36 patients enrolled in this study received induction chemotherapy with capecitabine and oxaliplatin followed by chemoradiation with the same chemotherapy backbone. Camrelizumab was added from the time of all chemotherapy initiation. The pathologic complete response observed (33.3%) compared favorably to historical references. No new safety signals were identified. Current standards for resectable EGA include adjuvant nivolumab in patients who have residual disease at the time of resection post chemoradiation. This study demonstrated that the addition of immunotherapy earlier in the treatment course is safe and possibly efficacious. The prospective randomized phase 2/3 ECOG-ACRIN 2174 study will evaluate the addition of nivolumab to chemoradiation, as well as the addition of ipilimumab to nivolumab in the adjuvant setting, and will answer the question regarding the benefits of immunotherapy used earlier in the course of disease in a prospective randomized manner (NCT03604991).

The study by de Jongh and colleagues evaluated the pattern of lymph node metastasis after neoadjuvant chemotherapy with relation to the location of the primary gastric tumor. Tumors from 212 patients who were previously enrolled in the Dutch LOGICA trial comparing laparoscopy vs open D2 gastrectomy were included in this analysis. Although the primary tumor location (proximal vs distal) was associated with a higher frequency of metastasis to certain lymph node groups, this relationship was not exclusive. As such, the extent of lymphadenectomy should not depend on the primary location of the tumor and is not affected by neoadjuvant chemotherapy.

Additional References

1. Hofheinz R-D, Merx K, Haag GM, et al. FLOT versus FLOT/trastuzumab/pertuzumab perioperative therapy of human epidermal growth factor receptor 2–positive resectable esophagogastric adenocarcinoma: A randomized phase II trial of the AIO EGA Study Group. J Clin Oncol. 2022;40:3750-3761. Doi: 10.1200/JCO.22.00380

2. Janjigian YY, Kawazoe A, Yañez P, et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021;600:727-730. Doi: 10.1038/s41586-021-04161-3

3. Bang Y-J, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687-697. Doi: 10.1016/S0140-6736(10)61121-X

4. Safran HP, Winter K, Hilson D, et al. Trastuzumab with trimodality treatment for oesophageal adenocarcinoma with HER2 overexpression (NRG Oncology/RTOG 1010): A multicentre, randomised, phase 3 trial. Lancet Oncol. 2022;23:259-269. Doi: 10.1016/S1470-2045(21)00718-X

5. Tabernero J, Hoff PM, Shen L, et al. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): Final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018:19:1372-1384. Doi: 10.1016/S1470-2045(18)30481-9

6. Tang Z, Wang Y, Liu D, et al. The Neo-PLANET phase II trial of neoadjuvant camrelizumab plus concurrent chemoradiotherapy in locally advanced adenocarcinoma of stomach or gastroesophageal junction. Nat Commun 2022;13:6807. Doi: 10.1038/s41467-022-34403-5

Research published during the past month focused mostly on sex differences, biomarkers, and treatment. Sex differences in psoriatic arthritis (PsA) are a significant focus of current research. One major question is how clinical features differ between men and women. Furer and colleagues investigated differences in musculoskeletal ultrasonographic features between men and women with PsA. In a prospective study including 70 men and 88 women, they demonstrated that although the total synovitis and tenosynovitis scores were similar between the two sexes, compared with women, men had higher total ultrasound and gray scale enthesitis scores (both P = .01) and sonographic active inflammatory score (P = .005). Given the uncertainty associated with the clinical diagnosis of enthesitis, this study emphasizes the importance of careful ultrasonographic evaluation when evaluating enthesitis patients, especially women.

It is important to investigate pregnancy outcomes in women with inflammatory arthritis, including PsA, to appropriately counsel and manage patients in the reproductive-age group. Preeclampsia is an important pregnancy outcome that is less well studied in PsA. Secher and colleagues analyzed data from registries in Sweden and Denmark that included singleton pregnant women with rheumatoid arthritis (n = 1739), axial spondyloarthritis (n = 819), and PsA (n = 489) who were matched with 17,390, 8190, and 4890 control pregnant women, respectively. They found that compared with the control women, the risk for preeclampsia was much higher in women with PsA (adjusted odds ratio [aOR; adjusted for country, maternal age, parity, year of delivery, body mass index (BMI), smoking, and education] 1.85; 95% CI 1.10-3.12), with the risk being primarily driven by the receipt of monotherapy for PsA before pregnancy (aOR 2.72; 95% CI 1.44-5.13), probably reflecting the presence of more severe disease. Women with PsA who tend to have higher BMI and active disease need to be counseled about the risk for preeclampsia and be carefully monitored.

The Disease Activity index for PsA (DAPSA) is a validated instrument used in clinical practice to assess PsA disease activity. One drawback of this instrument is that it requires testing for C-reactive protein (CRP), the results of which may not be available immediately, making it difficult to use DAPSA for implementing treating-to-target strategies during a clinic visit. To alleviate this issue, a quick quantitative CRP (qCRP) assay was developed. In a multicenter, cross-sectional study including 104 patients with PsA and available CRP values (measured by routine laboratory and qCRP assays), Proft and colleagues demonstrated that 98.1% of patients were similarly categorized into disease activity groups (remission and low, moderate, and high disease activity) using DAPSA based on qCRP (Q-DAPSA) and DAPSA. The agreement between the two instruments was excellent (weighted Cohen kappa 0.980; 95% CI 0.952-1.000). Thus, the Q-DAPSA may be used in place of DAPSA when evaluating PsA disease activity.

Regarding treatment, in an exploratory analysis of SELECT-PsA 1, McInnes and colleagues demonstrated that, at week 104, a similar proportion of patients receiving 15/30 mg upadacitinib vs adalimumab achieved ≥ 20% improvement in the American College of Rheumatology (ACR20) criteria (69.0%/69.5% vs 63.4%), whereas significantly more patients receiving 30 mg upadacitinib vs adalimumab achieved minimal disease activity (45.9% vs 37.8%; P < .05). The safety profiles of upadacitinib and adalimumab were comparable. Moreover, analyses of 52-week outcome data from the ongoing phase 3 KEEPsAKE 1 study of risankizumab (IL-23 inhibitor) by Kristensen and colleagues showed that among patients who received risankizumab continuously, the ACR20 response increased from 57.3% at week 24 to 70.0% at week 52. No new safety signals were identified. Thus, upadacitinib and risankizumab are newer, safe, and effective disease-modifying antirheumatic drugs for PsA.

Research published during the past month focused mostly on sex differences, biomarkers, and treatment. Sex differences in psoriatic arthritis (PsA) are a significant focus of current research. One major question is how clinical features differ between men and women. Furer and colleagues investigated differences in musculoskeletal ultrasonographic features between men and women with PsA. In a prospective study including 70 men and 88 women, they demonstrated that although the total synovitis and tenosynovitis scores were similar between the two sexes, compared with women, men had higher total ultrasound and gray scale enthesitis scores (both P = .01) and sonographic active inflammatory score (P = .005). Given the uncertainty associated with the clinical diagnosis of enthesitis, this study emphasizes the importance of careful ultrasonographic evaluation when evaluating enthesitis patients, especially women.

It is important to investigate pregnancy outcomes in women with inflammatory arthritis, including PsA, to appropriately counsel and manage patients in the reproductive-age group. Preeclampsia is an important pregnancy outcome that is less well studied in PsA. Secher and colleagues analyzed data from registries in Sweden and Denmark that included singleton pregnant women with rheumatoid arthritis (n = 1739), axial spondyloarthritis (n = 819), and PsA (n = 489) who were matched with 17,390, 8190, and 4890 control pregnant women, respectively. They found that compared with the control women, the risk for preeclampsia was much higher in women with PsA (adjusted odds ratio [aOR; adjusted for country, maternal age, parity, year of delivery, body mass index (BMI), smoking, and education] 1.85; 95% CI 1.10-3.12), with the risk being primarily driven by the receipt of monotherapy for PsA before pregnancy (aOR 2.72; 95% CI 1.44-5.13), probably reflecting the presence of more severe disease. Women with PsA who tend to have higher BMI and active disease need to be counseled about the risk for preeclampsia and be carefully monitored.

The Disease Activity index for PsA (DAPSA) is a validated instrument used in clinical practice to assess PsA disease activity. One drawback of this instrument is that it requires testing for C-reactive protein (CRP), the results of which may not be available immediately, making it difficult to use DAPSA for implementing treating-to-target strategies during a clinic visit. To alleviate this issue, a quick quantitative CRP (qCRP) assay was developed. In a multicenter, cross-sectional study including 104 patients with PsA and available CRP values (measured by routine laboratory and qCRP assays), Proft and colleagues demonstrated that 98.1% of patients were similarly categorized into disease activity groups (remission and low, moderate, and high disease activity) using DAPSA based on qCRP (Q-DAPSA) and DAPSA. The agreement between the two instruments was excellent (weighted Cohen kappa 0.980; 95% CI 0.952-1.000). Thus, the Q-DAPSA may be used in place of DAPSA when evaluating PsA disease activity.

Regarding treatment, in an exploratory analysis of SELECT-PsA 1, McInnes and colleagues demonstrated that, at week 104, a similar proportion of patients receiving 15/30 mg upadacitinib vs adalimumab achieved ≥ 20% improvement in the American College of Rheumatology (ACR20) criteria (69.0%/69.5% vs 63.4%), whereas significantly more patients receiving 30 mg upadacitinib vs adalimumab achieved minimal disease activity (45.9% vs 37.8%; P < .05). The safety profiles of upadacitinib and adalimumab were comparable. Moreover, analyses of 52-week outcome data from the ongoing phase 3 KEEPsAKE 1 study of risankizumab (IL-23 inhibitor) by Kristensen and colleagues showed that among patients who received risankizumab continuously, the ACR20 response increased from 57.3% at week 24 to 70.0% at week 52. No new safety signals were identified. Thus, upadacitinib and risankizumab are newer, safe, and effective disease-modifying antirheumatic drugs for PsA.

Research published during the past month focused mostly on sex differences, biomarkers, and treatment. Sex differences in psoriatic arthritis (PsA) are a significant focus of current research. One major question is how clinical features differ between men and women. Furer and colleagues investigated differences in musculoskeletal ultrasonographic features between men and women with PsA. In a prospective study including 70 men and 88 women, they demonstrated that although the total synovitis and tenosynovitis scores were similar between the two sexes, compared with women, men had higher total ultrasound and gray scale enthesitis scores (both P = .01) and sonographic active inflammatory score (P = .005). Given the uncertainty associated with the clinical diagnosis of enthesitis, this study emphasizes the importance of careful ultrasonographic evaluation when evaluating enthesitis patients, especially women.

It is important to investigate pregnancy outcomes in women with inflammatory arthritis, including PsA, to appropriately counsel and manage patients in the reproductive-age group. Preeclampsia is an important pregnancy outcome that is less well studied in PsA. Secher and colleagues analyzed data from registries in Sweden and Denmark that included singleton pregnant women with rheumatoid arthritis (n = 1739), axial spondyloarthritis (n = 819), and PsA (n = 489) who were matched with 17,390, 8190, and 4890 control pregnant women, respectively. They found that compared with the control women, the risk for preeclampsia was much higher in women with PsA (adjusted odds ratio [aOR; adjusted for country, maternal age, parity, year of delivery, body mass index (BMI), smoking, and education] 1.85; 95% CI 1.10-3.12), with the risk being primarily driven by the receipt of monotherapy for PsA before pregnancy (aOR 2.72; 95% CI 1.44-5.13), probably reflecting the presence of more severe disease. Women with PsA who tend to have higher BMI and active disease need to be counseled about the risk for preeclampsia and be carefully monitored.

The Disease Activity index for PsA (DAPSA) is a validated instrument used in clinical practice to assess PsA disease activity. One drawback of this instrument is that it requires testing for C-reactive protein (CRP), the results of which may not be available immediately, making it difficult to use DAPSA for implementing treating-to-target strategies during a clinic visit. To alleviate this issue, a quick quantitative CRP (qCRP) assay was developed. In a multicenter, cross-sectional study including 104 patients with PsA and available CRP values (measured by routine laboratory and qCRP assays), Proft and colleagues demonstrated that 98.1% of patients were similarly categorized into disease activity groups (remission and low, moderate, and high disease activity) using DAPSA based on qCRP (Q-DAPSA) and DAPSA. The agreement between the two instruments was excellent (weighted Cohen kappa 0.980; 95% CI 0.952-1.000). Thus, the Q-DAPSA may be used in place of DAPSA when evaluating PsA disease activity.

Regarding treatment, in an exploratory analysis of SELECT-PsA 1, McInnes and colleagues demonstrated that, at week 104, a similar proportion of patients receiving 15/30 mg upadacitinib vs adalimumab achieved ≥ 20% improvement in the American College of Rheumatology (ACR20) criteria (69.0%/69.5% vs 63.4%), whereas significantly more patients receiving 30 mg upadacitinib vs adalimumab achieved minimal disease activity (45.9% vs 37.8%; P < .05). The safety profiles of upadacitinib and adalimumab were comparable. Moreover, analyses of 52-week outcome data from the ongoing phase 3 KEEPsAKE 1 study of risankizumab (IL-23 inhibitor) by Kristensen and colleagues showed that among patients who received risankizumab continuously, the ACR20 response increased from 57.3% at week 24 to 70.0% at week 52. No new safety signals were identified. Thus, upadacitinib and risankizumab are newer, safe, and effective disease-modifying antirheumatic drugs for PsA.

Stable slate gray to blue lesions that are asymptomatic raise the possibility of a blue nevus, also known as dermal dendritic melanocytic proliferations. In this case, dermoscopy confirmed a uniform dark color with no signs suggestive of melanoma or pigmented basal cell carcinoma (BCC).

Blue nevi are the result of a benign localized proliferation of dermal dendritic melanocytes. The blue color is due to the increased pigment deep in the dermis that reflects the blue shorter wavelength light while absorbing longer wavelengths.¹ In this author’s experience, these “blue” lesions usually appear to be more gray (as was the case with this individual). Dermoscopy shows a steel blue homogenous pigmentation.²

It is helpful to use dermoscopy to screen for an atypical pigment network, regression of pigmentation, or abnormal pigmentation; these are signs of atypical nevi and melanoma. It is also important to look for arborizing blood vessels and leaf-like structures that can be seen in pigmented BCCs. Both melanoma and pigmented BCCs can appear as circumscribed dark lesions.

Reassuring factors for blue nevi are lesions that are stable in size and color over time, asymptomatic, and have not bled nor shown signs of erosion. If the diagnosis is in doubt, excise the lesion in its entirety for definitive pathology. Since the melanocytes are typically deeper in blue nevi than in most other nevi, a deep shave technique may not remove the lesion in its entirety. A deeper than usual shave (or, if feasible, a full-thickness excision) may return better results with quicker healing.

This patient was advised of the benign nature of a blue nevus. He was counseled to watch for any changes in the lesion and to return for reevaluation if symptoms or changes occurred.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

Stable slate gray to blue lesions that are asymptomatic raise the possibility of a blue nevus, also known as dermal dendritic melanocytic proliferations. In this case, dermoscopy confirmed a uniform dark color with no signs suggestive of melanoma or pigmented basal cell carcinoma (BCC).

Blue nevi are the result of a benign localized proliferation of dermal dendritic melanocytes. The blue color is due to the increased pigment deep in the dermis that reflects the blue shorter wavelength light while absorbing longer wavelengths.¹ In this author’s experience, these “blue” lesions usually appear to be more gray (as was the case with this individual). Dermoscopy shows a steel blue homogenous pigmentation.²

It is helpful to use dermoscopy to screen for an atypical pigment network, regression of pigmentation, or abnormal pigmentation; these are signs of atypical nevi and melanoma. It is also important to look for arborizing blood vessels and leaf-like structures that can be seen in pigmented BCCs. Both melanoma and pigmented BCCs can appear as circumscribed dark lesions.

Reassuring factors for blue nevi are lesions that are stable in size and color over time, asymptomatic, and have not bled nor shown signs of erosion. If the diagnosis is in doubt, excise the lesion in its entirety for definitive pathology. Since the melanocytes are typically deeper in blue nevi than in most other nevi, a deep shave technique may not remove the lesion in its entirety. A deeper than usual shave (or, if feasible, a full-thickness excision) may return better results with quicker healing.

This patient was advised of the benign nature of a blue nevus. He was counseled to watch for any changes in the lesion and to return for reevaluation if symptoms or changes occurred.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

Stable slate gray to blue lesions that are asymptomatic raise the possibility of a blue nevus, also known as dermal dendritic melanocytic proliferations. In this case, dermoscopy confirmed a uniform dark color with no signs suggestive of melanoma or pigmented basal cell carcinoma (BCC).

Blue nevi are the result of a benign localized proliferation of dermal dendritic melanocytes. The blue color is due to the increased pigment deep in the dermis that reflects the blue shorter wavelength light while absorbing longer wavelengths.¹ In this author’s experience, these “blue” lesions usually appear to be more gray (as was the case with this individual). Dermoscopy shows a steel blue homogenous pigmentation.²

It is helpful to use dermoscopy to screen for an atypical pigment network, regression of pigmentation, or abnormal pigmentation; these are signs of atypical nevi and melanoma. It is also important to look for arborizing blood vessels and leaf-like structures that can be seen in pigmented BCCs. Both melanoma and pigmented BCCs can appear as circumscribed dark lesions.

Reassuring factors for blue nevi are lesions that are stable in size and color over time, asymptomatic, and have not bled nor shown signs of erosion. If the diagnosis is in doubt, excise the lesion in its entirety for definitive pathology. Since the melanocytes are typically deeper in blue nevi than in most other nevi, a deep shave technique may not remove the lesion in its entirety. A deeper than usual shave (or, if feasible, a full-thickness excision) may return better results with quicker healing.

This patient was advised of the benign nature of a blue nevus. He was counseled to watch for any changes in the lesion and to return for reevaluation if symptoms or changes occurred.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

Hatanaka and colleagues investigated whether the etiology of the underlying liver disease affected the efficacy of atezolizumab and bevacizumab (A/B). They reported the results of a retrospective cohort study of 323 patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C hepatocellular carcinoma and Child-Pugh class A cirrhosis who started A/B between September 2020 and December 2021. Patients with viral infection were defined as those who were either serum anti–hepatitis C antibody (anti-HCV Ab)- or hepatitis B surface antigen (HBs-Ag)-positive, while patients with nonviral infection was defined as those who were both serum anti-HCV Ab- and HBs-Ag-negative. After propensity matching, no significant difference in response rate ([RR] 20.6% vs 24.6% in viral and nonviral patients), disease control rate (68.3% vs 69.0%), progression-free survival ([PFS] 7.0 months vs 6.2 months), or 12-month overall survival ([OS] 65.5% vs 71.7%) was seen. The authors concluded that the underlying etiology of liver disease in patients with HCC does not affect the response to treatment with A/B.

Scheiner and colleagues evaluated the efficacy of immunotherapy in patients with HCC who had already received immune checkpoint inhibitors (ICI) in a previous line of therapy. The authors reported the results of an international, retrospective multicenter study of 58 patients with HCC who received at least two lines of ICI-based therapies. The first ICI was discontinued due to disease progression in 90%. Nonetheless, the RR to the second ICI was 26% (compared with 22% for the first ICI), with a time-to-progression (TTP) of 5.4 months (95% CI, 3.0-7.7) for the first ICI and 5.2 months (95% CI, 3.3-7.0) for the second ICI. Grade 3/4 treatment-related adverse events were observed in 16% and 17% of patients with the first and second ICI, respectively. Therefore, the authors believe that ICI rechallenge is safe and results in a treatment benefit for a similar proportion of HCC patients, as is seen with the first ICI treatment. They suggest that ICI-based regimens should be studied in prospective trials of patients who progressed on first-line immunotherapy.

Finally, Kim and colleagues reported outcomes of patients who developed anti-drug antibodies (ADA) against atezolizumab while on A/B. In this prospective cohort study, 174 patients with advanced HCC who were treated with first-line A/B were tested for serum ADA levels prior to treatment and at 3 weeks (cycle 2 day 1 [C2D1]). Clinically, patients with progressive disease exhibited higher ADA levels (median 65.2 [0-520.4] ng/mL) at C2D1 than responders (0-117.5 ng/mL). Patients with high ADA levels at C2D1 had a reduced response rate (29%-34% vs 7-11%) and worse PFS and OS. The investigators found that very high ADA levels (≥ 1000 ng/mL) at 3 weeks were consistently associated with poor clinical outcomes due to reduced systemic exposure to atezolizumab and impaired proliferation and activation of peripheral CD8-positive T cells. They suggested future validation and standardization of ADA assays to optimize treatment with atezolizumab in patients with uHCC.

Hatanaka and colleagues investigated whether the etiology of the underlying liver disease affected the efficacy of atezolizumab and bevacizumab (A/B). They reported the results of a retrospective cohort study of 323 patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C hepatocellular carcinoma and Child-Pugh class A cirrhosis who started A/B between September 2020 and December 2021. Patients with viral infection were defined as those who were either serum anti–hepatitis C antibody (anti-HCV Ab)- or hepatitis B surface antigen (HBs-Ag)-positive, while patients with nonviral infection was defined as those who were both serum anti-HCV Ab- and HBs-Ag-negative. After propensity matching, no significant difference in response rate ([RR] 20.6% vs 24.6% in viral and nonviral patients), disease control rate (68.3% vs 69.0%), progression-free survival ([PFS] 7.0 months vs 6.2 months), or 12-month overall survival ([OS] 65.5% vs 71.7%) was seen. The authors concluded that the underlying etiology of liver disease in patients with HCC does not affect the response to treatment with A/B.

Scheiner and colleagues evaluated the efficacy of immunotherapy in patients with HCC who had already received immune checkpoint inhibitors (ICI) in a previous line of therapy. The authors reported the results of an international, retrospective multicenter study of 58 patients with HCC who received at least two lines of ICI-based therapies. The first ICI was discontinued due to disease progression in 90%. Nonetheless, the RR to the second ICI was 26% (compared with 22% for the first ICI), with a time-to-progression (TTP) of 5.4 months (95% CI, 3.0-7.7) for the first ICI and 5.2 months (95% CI, 3.3-7.0) for the second ICI. Grade 3/4 treatment-related adverse events were observed in 16% and 17% of patients with the first and second ICI, respectively. Therefore, the authors believe that ICI rechallenge is safe and results in a treatment benefit for a similar proportion of HCC patients, as is seen with the first ICI treatment. They suggest that ICI-based regimens should be studied in prospective trials of patients who progressed on first-line immunotherapy.

Finally, Kim and colleagues reported outcomes of patients who developed anti-drug antibodies (ADA) against atezolizumab while on A/B. In this prospective cohort study, 174 patients with advanced HCC who were treated with first-line A/B were tested for serum ADA levels prior to treatment and at 3 weeks (cycle 2 day 1 [C2D1]). Clinically, patients with progressive disease exhibited higher ADA levels (median 65.2 [0-520.4] ng/mL) at C2D1 than responders (0-117.5 ng/mL). Patients with high ADA levels at C2D1 had a reduced response rate (29%-34% vs 7-11%) and worse PFS and OS. The investigators found that very high ADA levels (≥ 1000 ng/mL) at 3 weeks were consistently associated with poor clinical outcomes due to reduced systemic exposure to atezolizumab and impaired proliferation and activation of peripheral CD8-positive T cells. They suggested future validation and standardization of ADA assays to optimize treatment with atezolizumab in patients with uHCC.

Hatanaka and colleagues investigated whether the etiology of the underlying liver disease affected the efficacy of atezolizumab and bevacizumab (A/B). They reported the results of a retrospective cohort study of 323 patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C hepatocellular carcinoma and Child-Pugh class A cirrhosis who started A/B between September 2020 and December 2021. Patients with viral infection were defined as those who were either serum anti–hepatitis C antibody (anti-HCV Ab)- or hepatitis B surface antigen (HBs-Ag)-positive, while patients with nonviral infection was defined as those who were both serum anti-HCV Ab- and HBs-Ag-negative. After propensity matching, no significant difference in response rate ([RR] 20.6% vs 24.6% in viral and nonviral patients), disease control rate (68.3% vs 69.0%), progression-free survival ([PFS] 7.0 months vs 6.2 months), or 12-month overall survival ([OS] 65.5% vs 71.7%) was seen. The authors concluded that the underlying etiology of liver disease in patients with HCC does not affect the response to treatment with A/B.

Scheiner and colleagues evaluated the efficacy of immunotherapy in patients with HCC who had already received immune checkpoint inhibitors (ICI) in a previous line of therapy. The authors reported the results of an international, retrospective multicenter study of 58 patients with HCC who received at least two lines of ICI-based therapies. The first ICI was discontinued due to disease progression in 90%. Nonetheless, the RR to the second ICI was 26% (compared with 22% for the first ICI), with a time-to-progression (TTP) of 5.4 months (95% CI, 3.0-7.7) for the first ICI and 5.2 months (95% CI, 3.3-7.0) for the second ICI. Grade 3/4 treatment-related adverse events were observed in 16% and 17% of patients with the first and second ICI, respectively. Therefore, the authors believe that ICI rechallenge is safe and results in a treatment benefit for a similar proportion of HCC patients, as is seen with the first ICI treatment. They suggest that ICI-based regimens should be studied in prospective trials of patients who progressed on first-line immunotherapy.

Finally, Kim and colleagues reported outcomes of patients who developed anti-drug antibodies (ADA) against atezolizumab while on A/B. In this prospective cohort study, 174 patients with advanced HCC who were treated with first-line A/B were tested for serum ADA levels prior to treatment and at 3 weeks (cycle 2 day 1 [C2D1]). Clinically, patients with progressive disease exhibited higher ADA levels (median 65.2 [0-520.4] ng/mL) at C2D1 than responders (0-117.5 ng/mL). Patients with high ADA levels at C2D1 had a reduced response rate (29%-34% vs 7-11%) and worse PFS and OS. The investigators found that very high ADA levels (≥ 1000 ng/mL) at 3 weeks were consistently associated with poor clinical outcomes due to reduced systemic exposure to atezolizumab and impaired proliferation and activation of peripheral CD8-positive T cells. They suggested future validation and standardization of ADA assays to optimize treatment with atezolizumab in patients with uHCC.

Hatanaka and colleagues investigated whether the etiology of the underlying liver disease affected the efficacy of atezolizumab and bevacizumab (A/B). They reported the results of a retrospective cohort study of 323 patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C hepatocellular carcinoma and Child-Pugh class A cirrhosis who started A/B between September 2020 and December 2021. Patients with viral infection were defined as those who were either serum anti–hepatitis C antibody (anti-HCV Ab)- or hepatitis B surface antigen (HBs-Ag)-positive, while patients with nonviral infection was defined as those who were both serum anti-HCV Ab- and HBs-Ag-negative. After propensity matching, no significant difference in response rate ([RR] 20.6% vs 24.6% in viral and nonviral patients), disease control rate (68.3% vs 69.0%), progression-free survival ([PFS] 7.0 months vs 6.2 months), or 12-month overall survival ([OS] 65.5% vs 71.7%) was seen. The authors concluded that the underlying etiology of liver disease in patients with HCC does not affect the response to treatment with A/B.

Scheiner and colleagues evaluated the efficacy of immunotherapy in patients with HCC who had already received immune checkpoint inhibitors (ICI) in a previous line of therapy. The authors reported the results of an international, retrospective multicenter study of 58 patients with HCC who received at least two lines of ICI-based therapies. The first ICI was discontinued due to disease progression in 90%. Nonetheless, the RR to the second ICI was 26% (compared with 22% for the first ICI), with a time-to-progression (TTP) of 5.4 months (95% CI, 3.0-7.7) for the first ICI and 5.2 months (95% CI, 3.3-7.0) for the second ICI. Grade 3/4 treatment-related adverse events were observed in 16% and 17% of patients with the first and second ICI, respectively. Therefore, the authors believe that ICI rechallenge is safe and results in a treatment benefit for a similar proportion of HCC patients, as is seen with the first ICI treatment. They suggest that ICI-based regimens should be studied in prospective trials of patients who progressed on first-line immunotherapy.

Finally, Kim and colleagues reported outcomes of patients who developed anti-drug antibodies (ADA) against atezolizumab while on A/B. In this prospective cohort study, 174 patients with advanced HCC who were treated with first-line A/B were tested for serum ADA levels prior to treatment and at 3 weeks (cycle 2 day 1 [C2D1]). Clinically, patients with progressive disease exhibited higher ADA levels (median 65.2 [0-520.4] ng/mL) at C2D1 than responders (0-117.5 ng/mL). Patients with high ADA levels at C2D1 had a reduced response rate (29%-34% vs 7-11%) and worse PFS and OS. The investigators found that very high ADA levels (≥ 1000 ng/mL) at 3 weeks were consistently associated with poor clinical outcomes due to reduced systemic exposure to atezolizumab and impaired proliferation and activation of peripheral CD8-positive T cells. They suggested future validation and standardization of ADA assays to optimize treatment with atezolizumab in patients with uHCC.

Hatanaka and colleagues investigated whether the etiology of the underlying liver disease affected the efficacy of atezolizumab and bevacizumab (A/B). They reported the results of a retrospective cohort study of 323 patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C hepatocellular carcinoma and Child-Pugh class A cirrhosis who started A/B between September 2020 and December 2021. Patients with viral infection were defined as those who were either serum anti–hepatitis C antibody (anti-HCV Ab)- or hepatitis B surface antigen (HBs-Ag)-positive, while patients with nonviral infection was defined as those who were both serum anti-HCV Ab- and HBs-Ag-negative. After propensity matching, no significant difference in response rate ([RR] 20.6% vs 24.6% in viral and nonviral patients), disease control rate (68.3% vs 69.0%), progression-free survival ([PFS] 7.0 months vs 6.2 months), or 12-month overall survival ([OS] 65.5% vs 71.7%) was seen. The authors concluded that the underlying etiology of liver disease in patients with HCC does not affect the response to treatment with A/B.

Scheiner and colleagues evaluated the efficacy of immunotherapy in patients with HCC who had already received immune checkpoint inhibitors (ICI) in a previous line of therapy. The authors reported the results of an international, retrospective multicenter study of 58 patients with HCC who received at least two lines of ICI-based therapies. The first ICI was discontinued due to disease progression in 90%. Nonetheless, the RR to the second ICI was 26% (compared with 22% for the first ICI), with a time-to-progression (TTP) of 5.4 months (95% CI, 3.0-7.7) for the first ICI and 5.2 months (95% CI, 3.3-7.0) for the second ICI. Grade 3/4 treatment-related adverse events were observed in 16% and 17% of patients with the first and second ICI, respectively. Therefore, the authors believe that ICI rechallenge is safe and results in a treatment benefit for a similar proportion of HCC patients, as is seen with the first ICI treatment. They suggest that ICI-based regimens should be studied in prospective trials of patients who progressed on first-line immunotherapy.

Finally, Kim and colleagues reported outcomes of patients who developed anti-drug antibodies (ADA) against atezolizumab while on A/B. In this prospective cohort study, 174 patients with advanced HCC who were treated with first-line A/B were tested for serum ADA levels prior to treatment and at 3 weeks (cycle 2 day 1 [C2D1]). Clinically, patients with progressive disease exhibited higher ADA levels (median 65.2 [0-520.4] ng/mL) at C2D1 than responders (0-117.5 ng/mL). Patients with high ADA levels at C2D1 had a reduced response rate (29%-34% vs 7-11%) and worse PFS and OS. The investigators found that very high ADA levels (≥ 1000 ng/mL) at 3 weeks were consistently associated with poor clinical outcomes due to reduced systemic exposure to atezolizumab and impaired proliferation and activation of peripheral CD8-positive T cells. They suggested future validation and standardization of ADA assays to optimize treatment with atezolizumab in patients with uHCC.

Hatanaka and colleagues investigated whether the etiology of the underlying liver disease affected the efficacy of atezolizumab and bevacizumab (A/B). They reported the results of a retrospective cohort study of 323 patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C hepatocellular carcinoma and Child-Pugh class A cirrhosis who started A/B between September 2020 and December 2021. Patients with viral infection were defined as those who were either serum anti–hepatitis C antibody (anti-HCV Ab)- or hepatitis B surface antigen (HBs-Ag)-positive, while patients with nonviral infection was defined as those who were both serum anti-HCV Ab- and HBs-Ag-negative. After propensity matching, no significant difference in response rate ([RR] 20.6% vs 24.6% in viral and nonviral patients), disease control rate (68.3% vs 69.0%), progression-free survival ([PFS] 7.0 months vs 6.2 months), or 12-month overall survival ([OS] 65.5% vs 71.7%) was seen. The authors concluded that the underlying etiology of liver disease in patients with HCC does not affect the response to treatment with A/B.

Scheiner and colleagues evaluated the efficacy of immunotherapy in patients with HCC who had already received immune checkpoint inhibitors (ICI) in a previous line of therapy. The authors reported the results of an international, retrospective multicenter study of 58 patients with HCC who received at least two lines of ICI-based therapies. The first ICI was discontinued due to disease progression in 90%. Nonetheless, the RR to the second ICI was 26% (compared with 22% for the first ICI), with a time-to-progression (TTP) of 5.4 months (95% CI, 3.0-7.7) for the first ICI and 5.2 months (95% CI, 3.3-7.0) for the second ICI. Grade 3/4 treatment-related adverse events were observed in 16% and 17% of patients with the first and second ICI, respectively. Therefore, the authors believe that ICI rechallenge is safe and results in a treatment benefit for a similar proportion of HCC patients, as is seen with the first ICI treatment. They suggest that ICI-based regimens should be studied in prospective trials of patients who progressed on first-line immunotherapy.

Finally, Kim and colleagues reported outcomes of patients who developed anti-drug antibodies (ADA) against atezolizumab while on A/B. In this prospective cohort study, 174 patients with advanced HCC who were treated with first-line A/B were tested for serum ADA levels prior to treatment and at 3 weeks (cycle 2 day 1 [C2D1]). Clinically, patients with progressive disease exhibited higher ADA levels (median 65.2 [0-520.4] ng/mL) at C2D1 than responders (0-117.5 ng/mL). Patients with high ADA levels at C2D1 had a reduced response rate (29%-34% vs 7-11%) and worse PFS and OS. The investigators found that very high ADA levels (≥ 1000 ng/mL) at 3 weeks were consistently associated with poor clinical outcomes due to reduced systemic exposure to atezolizumab and impaired proliferation and activation of peripheral CD8-positive T cells. They suggested future validation and standardization of ADA assays to optimize treatment with atezolizumab in patients with uHCC.

Taxanes are an integral component of various treatment regimens for all stages of breast cancer. As survival outcomes have improved, it has become increasingly important to focus on the long-term quality-of-life impact of treatment. Neurotoxicity is a well-recognized potential side effect of taxane chemotherapy. In a prospective cohort study including 1234 patients diagnosed with breast cancer and receiving taxanes, the risk for patient-reported chemotherapy-induced peripheral neuropathy (CIPN) were lower in the paclitaxel (HR 0.59; P = .008) and docetaxel (HR 0.65; P = .02) groups vs the nab-paclitaxel group. There was less sensory discomfort reported with paclitaxel (HR 0.44; P < .001) and docetaxel (HR 0.52; P < .001) vs nab-paclitaxel; however, reported motor and autonomic symptoms were not significantly lower than in the nab-paclitaxel group (Mo et al). An area of research interest is the identification of biomarkers that may predict a higher likelihood of CIPN development, to aid in early detection and intervention.³

Management strategies for breast cancer diagnosed in older women should take into consideration age and competing medical comorbidities, and hormone receptor–positive histology is the most common subtype in this population. Some older women may be too frail or unfit for surgery, and furthermore, some may prefer to avoid surgery, even if it is considered a safe approach. A retrospective study including 91 older (≥ 70 years) patients with estrogen receptor–positive (ER+) breast cancer who underwent definitive endocrine therapy demonstrated a twofold higher mortality risk than the risk of needing invasive local treatment (surgery or radiation). The 5-year cumulative risks of undergoing invasive local treatment and having uncontrolled disease were 28% and 16%, respectively, whereas the 5-year cumulative overall survival was 42% (Gooijer et al). Although the majority of older women with ER+ early breast cancer will obtain a survival benefit with surgery plus endocrine therapy compared with primary endocrine therapy, there is a selected group with limited life expectancy owing to age, functional status, or medical comorbidities for whom it is appropriate to offer primary endocrine therapy, because breast cancer–specific survival may not be negatively affected.⁴

Additional References

1. Schmid P, Cortes J, Dent R, et al; for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. Doi: 10.1056/NEJMoa2112651
2. Harbeck N, Rastogi P, Martin M, et al; on behalf of the monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015
3. Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of chemotherapy-induced peripheral neuropathy: current status and future directions. Front Pain Res (Lausanne). 2022;3:864910. Doi: 10.3389/fpain.2022.864910
4. Wyld L, Reed MW, Morgan J, et al. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life. Eur J Cancer. 2021;142:48-62. Doi: 10.1016/j.ejca.2020.10.015

Taxanes are an integral component of various treatment regimens for all stages of breast cancer. As survival outcomes have improved, it has become increasingly important to focus on the long-term quality-of-life impact of treatment. Neurotoxicity is a well-recognized potential side effect of taxane chemotherapy. In a prospective cohort study including 1234 patients diagnosed with breast cancer and receiving taxanes, the risk for patient-reported chemotherapy-induced peripheral neuropathy (CIPN) were lower in the paclitaxel (HR 0.59; P = .008) and docetaxel (HR 0.65; P = .02) groups vs the nab-paclitaxel group. There was less sensory discomfort reported with paclitaxel (HR 0.44; P < .001) and docetaxel (HR 0.52; P < .001) vs nab-paclitaxel; however, reported motor and autonomic symptoms were not significantly lower than in the nab-paclitaxel group (Mo et al). An area of research interest is the identification of biomarkers that may predict a higher likelihood of CIPN development, to aid in early detection and intervention.³

Management strategies for breast cancer diagnosed in older women should take into consideration age and competing medical comorbidities, and hormone receptor–positive histology is the most common subtype in this population. Some older women may be too frail or unfit for surgery, and furthermore, some may prefer to avoid surgery, even if it is considered a safe approach. A retrospective study including 91 older (≥ 70 years) patients with estrogen receptor–positive (ER+) breast cancer who underwent definitive endocrine therapy demonstrated a twofold higher mortality risk than the risk of needing invasive local treatment (surgery or radiation). The 5-year cumulative risks of undergoing invasive local treatment and having uncontrolled disease were 28% and 16%, respectively, whereas the 5-year cumulative overall survival was 42% (Gooijer et al). Although the majority of older women with ER+ early breast cancer will obtain a survival benefit with surgery plus endocrine therapy compared with primary endocrine therapy, there is a selected group with limited life expectancy owing to age, functional status, or medical comorbidities for whom it is appropriate to offer primary endocrine therapy, because breast cancer–specific survival may not be negatively affected.⁴

Additional References

1. Schmid P, Cortes J, Dent R, et al; for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. Doi: 10.1056/NEJMoa2112651
2. Harbeck N, Rastogi P, Martin M, et al; on behalf of the monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015
3. Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of chemotherapy-induced peripheral neuropathy: current status and future directions. Front Pain Res (Lausanne). 2022;3:864910. Doi: 10.3389/fpain.2022.864910
4. Wyld L, Reed MW, Morgan J, et al. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life. Eur J Cancer. 2021;142:48-62. Doi: 10.1016/j.ejca.2020.10.015

Taxanes are an integral component of various treatment regimens for all stages of breast cancer. As survival outcomes have improved, it has become increasingly important to focus on the long-term quality-of-life impact of treatment. Neurotoxicity is a well-recognized potential side effect of taxane chemotherapy. In a prospective cohort study including 1234 patients diagnosed with breast cancer and receiving taxanes, the risk for patient-reported chemotherapy-induced peripheral neuropathy (CIPN) were lower in the paclitaxel (HR 0.59; P = .008) and docetaxel (HR 0.65; P = .02) groups vs the nab-paclitaxel group. There was less sensory discomfort reported with paclitaxel (HR 0.44; P < .001) and docetaxel (HR 0.52; P < .001) vs nab-paclitaxel; however, reported motor and autonomic symptoms were not significantly lower than in the nab-paclitaxel group (Mo et al). An area of research interest is the identification of biomarkers that may predict a higher likelihood of CIPN development, to aid in early detection and intervention.³

Management strategies for breast cancer diagnosed in older women should take into consideration age and competing medical comorbidities, and hormone receptor–positive histology is the most common subtype in this population. Some older women may be too frail or unfit for surgery, and furthermore, some may prefer to avoid surgery, even if it is considered a safe approach. A retrospective study including 91 older (≥ 70 years) patients with estrogen receptor–positive (ER+) breast cancer who underwent definitive endocrine therapy demonstrated a twofold higher mortality risk than the risk of needing invasive local treatment (surgery or radiation). The 5-year cumulative risks of undergoing invasive local treatment and having uncontrolled disease were 28% and 16%, respectively, whereas the 5-year cumulative overall survival was 42% (Gooijer et al). Although the majority of older women with ER+ early breast cancer will obtain a survival benefit with surgery plus endocrine therapy compared with primary endocrine therapy, there is a selected group with limited life expectancy owing to age, functional status, or medical comorbidities for whom it is appropriate to offer primary endocrine therapy, because breast cancer–specific survival may not be negatively affected.⁴

Additional References

1. Schmid P, Cortes J, Dent R, et al; for the KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. Doi: 10.1056/NEJMoa2112651
2. Harbeck N, Rastogi P, Martin M, et al; on behalf of the monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015
3. Rodwin RL, Siddiq NZ, Ehrlich BE, Lustberg MB. Biomarkers of chemotherapy-induced peripheral neuropathy: current status and future directions. Front Pain Res (Lausanne). 2022;3:864910. Doi: 10.3389/fpain.2022.864910
4. Wyld L, Reed MW, Morgan J, et al. Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life. Eur J Cancer. 2021;142:48-62. Doi: 10.1016/j.ejca.2020.10.015

The safety of vaginal breech delivery has been controversial since the Term Breech Trial in 2000 suggested increased neonatal mortality and short-term morbidity associated with vaginal breech delivery. The stance against breech delivery has softened since that time. Fruscalzo and colleagues provide yet more evidence supporting the safety of vaginal breech deliveries with their single-center, retrospective study, which included 804 singleton pregnant women who underwent vaginal breech vs emergency cesarean section vs elective cesarean section in Coesfeld, Germany. They found no significant differences between the vaginal breech–delivery group vs the other two groups in regard to umbilical artery pH < 7, low Apgar scores, or neonatal intensive care unit admissions. The only significant difference noted was umbilical artery pH < 7.1. This suggests that in experienced hands (each of the candidates was referred to a senior obstetrician for consultation), vaginal breech delivery can be safe, including for nulliparous women (67% were nulliparous), showing that even the short-term morbidity associated with vaginal breech delivery approaches that of planned cesarean section.

Two other articles raise caution regarding SD and increased risk for fetal death and PPH. Linde and colleagues used data from The Medical Birth Registry of Norway and Statistics Norway to examine recurrence risk for PPH associated with various causes. PPH associated with SD led the way: The recurrence risk adjusted odds ratio (aOR) was 6.8 for SD vs 5.9 for retained products of conception, 4.0 for uterine atony, 3.9 for obstetric trauma, and 2.2 for PPH of undefined cause. This study suggests that the risks for SD recurrence should be focused not just on SD, but also on PPH. Another concern regarding shoulder dystocia is raised by Davidesko and colleagues in their analysis of risk factors for intrapartum fetal death. Using a generalized estimation equation model to help identify independent risk factors for intrapartum fetal death, they examined 344,536 deliveries from 1991 to 2016 at Soroka University Medical Center in Israel and noted that SD again led the way: aOR was 23.8 for SD vs 19.0 for uterine rupture, 11.9 for preterm birth, 6.2 for placental abruption, and 3.6 for fetal malpresentation. This high risk for intrapartum fetal death associated with SD suggests a need for even more robust SD drills to help deal with this dreaded and often unpredictable obstetric emergency.

The safety of vaginal breech delivery has been controversial since the Term Breech Trial in 2000 suggested increased neonatal mortality and short-term morbidity associated with vaginal breech delivery. The stance against breech delivery has softened since that time. Fruscalzo and colleagues provide yet more evidence supporting the safety of vaginal breech deliveries with their single-center, retrospective study, which included 804 singleton pregnant women who underwent vaginal breech vs emergency cesarean section vs elective cesarean section in Coesfeld, Germany. They found no significant differences between the vaginal breech–delivery group vs the other two groups in regard to umbilical artery pH < 7, low Apgar scores, or neonatal intensive care unit admissions. The only significant difference noted was umbilical artery pH < 7.1. This suggests that in experienced hands (each of the candidates was referred to a senior obstetrician for consultation), vaginal breech delivery can be safe, including for nulliparous women (67% were nulliparous), showing that even the short-term morbidity associated with vaginal breech delivery approaches that of planned cesarean section.

Two other articles raise caution regarding SD and increased risk for fetal death and PPH. Linde and colleagues used data from The Medical Birth Registry of Norway and Statistics Norway to examine recurrence risk for PPH associated with various causes. PPH associated with SD led the way: The recurrence risk adjusted odds ratio (aOR) was 6.8 for SD vs 5.9 for retained products of conception, 4.0 for uterine atony, 3.9 for obstetric trauma, and 2.2 for PPH of undefined cause. This study suggests that the risks for SD recurrence should be focused not just on SD, but also on PPH. Another concern regarding shoulder dystocia is raised by Davidesko and colleagues in their analysis of risk factors for intrapartum fetal death. Using a generalized estimation equation model to help identify independent risk factors for intrapartum fetal death, they examined 344,536 deliveries from 1991 to 2016 at Soroka University Medical Center in Israel and noted that SD again led the way: aOR was 23.8 for SD vs 19.0 for uterine rupture, 11.9 for preterm birth, 6.2 for placental abruption, and 3.6 for fetal malpresentation. This high risk for intrapartum fetal death associated with SD suggests a need for even more robust SD drills to help deal with this dreaded and often unpredictable obstetric emergency.

The safety of vaginal breech delivery has been controversial since the Term Breech Trial in 2000 suggested increased neonatal mortality and short-term morbidity associated with vaginal breech delivery. The stance against breech delivery has softened since that time. Fruscalzo and colleagues provide yet more evidence supporting the safety of vaginal breech deliveries with their single-center, retrospective study, which included 804 singleton pregnant women who underwent vaginal breech vs emergency cesarean section vs elective cesarean section in Coesfeld, Germany. They found no significant differences between the vaginal breech–delivery group vs the other two groups in regard to umbilical artery pH < 7, low Apgar scores, or neonatal intensive care unit admissions. The only significant difference noted was umbilical artery pH < 7.1. This suggests that in experienced hands (each of the candidates was referred to a senior obstetrician for consultation), vaginal breech delivery can be safe, including for nulliparous women (67% were nulliparous), showing that even the short-term morbidity associated with vaginal breech delivery approaches that of planned cesarean section.

Two other articles raise caution regarding SD and increased risk for fetal death and PPH. Linde and colleagues used data from The Medical Birth Registry of Norway and Statistics Norway to examine recurrence risk for PPH associated with various causes. PPH associated with SD led the way: The recurrence risk adjusted odds ratio (aOR) was 6.8 for SD vs 5.9 for retained products of conception, 4.0 for uterine atony, 3.9 for obstetric trauma, and 2.2 for PPH of undefined cause. This study suggests that the risks for SD recurrence should be focused not just on SD, but also on PPH. Another concern regarding shoulder dystocia is raised by Davidesko and colleagues in their analysis of risk factors for intrapartum fetal death. Using a generalized estimation equation model to help identify independent risk factors for intrapartum fetal death, they examined 344,536 deliveries from 1991 to 2016 at Soroka University Medical Center in Israel and noted that SD again led the way: aOR was 23.8 for SD vs 19.0 for uterine rupture, 11.9 for preterm birth, 6.2 for placental abruption, and 3.6 for fetal malpresentation. This high risk for intrapartum fetal death associated with SD suggests a need for even more robust SD drills to help deal with this dreaded and often unpredictable obstetric emergency.

On November 1, the US Preventive Services Task Force (USPSTF) published updated recommendations (and a supporting evidence report) for the use of hormone therapy in postmenopausal women for the prevention of chronic medical conditions, such as heart disease, cancer, and osteoporosis.^1,2 The USPSTF continues to recommend against the use of either estrogen or combined estrogen plus progesterone for this purpose.

A bit of context. These recommendations apply to asymptomatic postmenopausal women and do not apply to those who are unable to manage menopausal symptoms (eg, hot flashes or vaginal dryness) with other interventions, or to those who have premature or surgically caused menopause.

This update is a reconfirmation of USPSTF’s 2017 recommendations on this topic. These recommendations are consistent with those of multiple other organizations, including the American College of Obstetricians and Gynecologists, the American Academy of Family Physicians, the American College of Physicians, and the American Heart Association.

A look at the evidence. The evidence report included data from 20 randomized clinical trials and 3 cohort studies that examined the use of oral or transdermal hormone therapy. The most commonly used therapy was oral conjugated equine estrogen 0.625 mg/d, with or without medroxyprogesterone acetate 2.5 mg/d. The strongest evidence is from the Women’s Health Initiative, which included postmenopausal women ages 50 to 79 years and had follow-up of 7.2 years for the estrogen-only trial, 5.6 years for the estrogen plus progestin trial, and a long-term follow-up of up to 20.7 years.^2,3

Benefits and harms of hormone therapy. Among postmenopausal women, use of estrogen alone was associated with absolute reduction in risk for fractures (–388 per 10,000 women), diabetes (–134), and breast cancer (–52) and an absolute increase in risk for urinary incontinence (+ 885 per 10,000 women), gallbladder disease (+ 377), stroke (+ 79), and venous thromboembolism (+ 77). Use of estrogen plus progestin was associated with reduced risk for fractures (–230 per 10,000 women), diabetes (–78), and colorectal cancer (–34) and an increased risk for urinary incontinence ( + 562 per 10,000 women), gallbladder disease (+ 260), venous thromboembolism (+ 120), dementia (+ 88), stroke (+ 52), and breast cancer (+ 51).^2,3

Lingering questions. The USPSTF felt that the evidence is too limited to answer the following: (1) Are the potential benefits and harms of hormone therapy affected by participants’ age or by the timing of therapy initiation in relation to menopause onset? and (2) Do different types, doses, or delivery modes of hormone therapy affect benefits and harms?¹

The bottom line. In asymptomatic, healthy, postmenopausal women, do not prescribe hormone therapy to try to prevent chronic conditions.

On November 1, the US Preventive Services Task Force (USPSTF) published updated recommendations (and a supporting evidence report) for the use of hormone therapy in postmenopausal women for the prevention of chronic medical conditions, such as heart disease, cancer, and osteoporosis.^1,2 The USPSTF continues to recommend against the use of either estrogen or combined estrogen plus progesterone for this purpose.

A bit of context. These recommendations apply to asymptomatic postmenopausal women and do not apply to those who are unable to manage menopausal symptoms (eg, hot flashes or vaginal dryness) with other interventions, or to those who have premature or surgically caused menopause.

This update is a reconfirmation of USPSTF’s 2017 recommendations on this topic. These recommendations are consistent with those of multiple other organizations, including the American College of Obstetricians and Gynecologists, the American Academy of Family Physicians, the American College of Physicians, and the American Heart Association.

A look at the evidence. The evidence report included data from 20 randomized clinical trials and 3 cohort studies that examined the use of oral or transdermal hormone therapy. The most commonly used therapy was oral conjugated equine estrogen 0.625 mg/d, with or without medroxyprogesterone acetate 2.5 mg/d. The strongest evidence is from the Women’s Health Initiative, which included postmenopausal women ages 50 to 79 years and had follow-up of 7.2 years for the estrogen-only trial, 5.6 years for the estrogen plus progestin trial, and a long-term follow-up of up to 20.7 years.^2,3

Benefits and harms of hormone therapy. Among postmenopausal women, use of estrogen alone was associated with absolute reduction in risk for fractures (–388 per 10,000 women), diabetes (–134), and breast cancer (–52) and an absolute increase in risk for urinary incontinence (+ 885 per 10,000 women), gallbladder disease (+ 377), stroke (+ 79), and venous thromboembolism (+ 77). Use of estrogen plus progestin was associated with reduced risk for fractures (–230 per 10,000 women), diabetes (–78), and colorectal cancer (–34) and an increased risk for urinary incontinence ( + 562 per 10,000 women), gallbladder disease (+ 260), venous thromboembolism (+ 120), dementia (+ 88), stroke (+ 52), and breast cancer (+ 51).^2,3

Lingering questions. The USPSTF felt that the evidence is too limited to answer the following: (1) Are the potential benefits and harms of hormone therapy affected by participants’ age or by the timing of therapy initiation in relation to menopause onset? and (2) Do different types, doses, or delivery modes of hormone therapy affect benefits and harms?¹

The bottom line. In asymptomatic, healthy, postmenopausal women, do not prescribe hormone therapy to try to prevent chronic conditions.

On November 1, the US Preventive Services Task Force (USPSTF) published updated recommendations (and a supporting evidence report) for the use of hormone therapy in postmenopausal women for the prevention of chronic medical conditions, such as heart disease, cancer, and osteoporosis.^1,2 The USPSTF continues to recommend against the use of either estrogen or combined estrogen plus progesterone for this purpose.

A bit of context. These recommendations apply to asymptomatic postmenopausal women and do not apply to those who are unable to manage menopausal symptoms (eg, hot flashes or vaginal dryness) with other interventions, or to those who have premature or surgically caused menopause.

This update is a reconfirmation of USPSTF’s 2017 recommendations on this topic. These recommendations are consistent with those of multiple other organizations, including the American College of Obstetricians and Gynecologists, the American Academy of Family Physicians, the American College of Physicians, and the American Heart Association.

A look at the evidence. The evidence report included data from 20 randomized clinical trials and 3 cohort studies that examined the use of oral or transdermal hormone therapy. The most commonly used therapy was oral conjugated equine estrogen 0.625 mg/d, with or without medroxyprogesterone acetate 2.5 mg/d. The strongest evidence is from the Women’s Health Initiative, which included postmenopausal women ages 50 to 79 years and had follow-up of 7.2 years for the estrogen-only trial, 5.6 years for the estrogen plus progestin trial, and a long-term follow-up of up to 20.7 years.^2,3

Benefits and harms of hormone therapy. Among postmenopausal women, use of estrogen alone was associated with absolute reduction in risk for fractures (–388 per 10,000 women), diabetes (–134), and breast cancer (–52) and an absolute increase in risk for urinary incontinence (+ 885 per 10,000 women), gallbladder disease (+ 377), stroke (+ 79), and venous thromboembolism (+ 77). Use of estrogen plus progestin was associated with reduced risk for fractures (–230 per 10,000 women), diabetes (–78), and colorectal cancer (–34) and an increased risk for urinary incontinence ( + 562 per 10,000 women), gallbladder disease (+ 260), venous thromboembolism (+ 120), dementia (+ 88), stroke (+ 52), and breast cancer (+ 51).^2,3

Lingering questions. The USPSTF felt that the evidence is too limited to answer the following: (1) Are the potential benefits and harms of hormone therapy affected by participants’ age or by the timing of therapy initiation in relation to menopause onset? and (2) Do different types, doses, or delivery modes of hormone therapy affect benefits and harms?¹

The bottom line. In asymptomatic, healthy, postmenopausal women, do not prescribe hormone therapy to try to prevent chronic conditions.