The
n e w e ng l a n d j o u r na l
of
m e dic i n e
pregnant women. The high risk of hepatitis E Jun Zhang, M.Sc. infection for travelers and health care and hu- J. Wai-Kuo Shih, Ph.D. manitarian relief workers who are deployed or Ning-Shao Xia traveling to areas where there is an ongoing Xiamen University School of Public Health China outbreak was also recognized. (It has been re- Xiamen, [email protected] ported that hepatitis E infection was diagnosed Since publication of their article, the authors report no furin health care workers from developed coun- ther potential conflict of interest. tries who had responded to outbreaks in refu- 1. Zhu F-C, Zhang J, Zhang X-F, et al. Efficacy and safety of a gee camps in Africa.3) In the absence of interna- recombinant hepatitis E vaccine in healthy adults: a large-scale, tional guidelines, the reliance on local regulatory randomised, double-blind placebo-controlled, phase 3 trial. Lancet 2010;376:895-902. agencies in outbreak countries that usually have 2. Hepatitis E Vaccine Working Group. Hepatitis E: epidemiology no capacity or experience to conduct qualified and disease burden. Geneva, World Health Organization, 2014 evaluations creates obstacles. In the meantime, (http://www.who.int/immunization/sage/meetings/2014/october/ 1_HEV_burden_paper_final_03_Oct_14_yellow_book.pdf?ua=1). the current manufacturer of the vaccine lacks 3. Hepatitis E vaccine: WHO position paper, May 2015. Wkly the resources to complete registration outside Epidemiol Rec 2015;90(18):185-200. China. One of the possible solutions is to 4. Nelson KE, Shih JW, Zhang J, et al. Hepatitis E vaccine to prevent morbidity and mortality during epidemics. Open Forum develop a ready-to-go preemptive protocol for Infect Dis 2014;1(3):ofu098. future outbreaks.4 DOI: 10.1056/NEJMc1504302
Outcomes of Pregnancy after Bariatric Surgery To the Editor: Johansson et al. (Feb. 26 issue)1 found that pregnancies after bariatric surgery are associated with reduced risks of gestational diabetes and large-for-gestational-age neonates as compared with control pregnancies in obese women. Perinatal mortality, however, was much higher than in the general Swedish population (1.7% vs. 0.4%).2 Both the article and the related editorial3 fail to mention surgical complications as a possible contributing factor. Small-bowel herniations after gastric bypass surgery may result in severe maternal and fetal complications.4 In an ongoing prospective cohort study (www.aurorastudy.org), 9 of 64 pregnant patients (14%) presented with gastric or abdominal symptoms, with 5 (8%) requiring surgery. It is plausible that this contributed to the increased prematurity rate and perinatal mortality in the Swedish cohort. Unfortunately, Johansson and colleagues did not report on obstetrical admissions and surgeries during pregnancy. In pregnant women who had previously undergone bariatric surgery, caregivers should be attentive to symptoms of internal herniation, such as abdominal pain and vomiting, which are often downplayed in pregnancy. Moreover, correct imaging techniques (i.e., computed tomography and magnetic resonance imaging) and operative intervention, which are often performed with reluctance in pregnant women, should not be delayed.5 2266
Roland Devlieger, M.D., Ph.D. Goele Jans, M.Sc. Christophe Matthys, Ph.D. KU Leuven Leuven, Belgium [email protected] No potential conflict of interest relevant to this letter was reported. 1. Johansson K, Cnattingius S, Näslund I, et al. Outcomes of
pregnancy after bariatric surgery. N Engl J Med 2015;372:814-24.
2. Stormdal Bring H, Hulthén Varli IA, Kublickas M, Papadogi-
annakis N, Pettersson K. Causes of stillbirth at different gestational ages in singleton pregnancies. Acta Obstet Gynecol Scand 2014;93:86-92. 3. Caughey AB. Bariatric surgery before pregnancy — is this a solution to a big problem? N Engl J Med 2015;372:877-8. 4. Guelinckx I, Devlieger R, Vansant G. Reproductive outcome after bariatric surgery: a critical review. Hum Reprod Update 2009;15:189-201. 5. Wax JR, Pinette MG, Cartin A. Roux-en-Y gastric bypassassociated bowel obstruction complicating pregnancy — an obstetrician’s map to the clinical minefield. Am J Obstet Gynecol 2013;208:265-71. DOI: 10.1056/NEJMc1503863
To the Editor: Johansson et al. reported important data about pregnancy outcomes after bariatric surgery. A concern is that measurement of 2-hour glucose levels during an oral glucose-tolerance test or after a meal is unsuitable for diagnosing gestational diabetes after gastric bypass surgery. Patients who have undergone this surgery have a very early glucose peak (within 1 hour
n engl j med 372;23 nejm.org june 4, 2015
The New England Journal of Medicine Downloaded from nejm.org at UC SHARED JOURNAL COLLECTION on June 4, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
correspondence
after carbohydrate loading), often followed by hyperinsulinemic hypoglycemia 1 to 3 hours after carbohydrate loading.1-3 This observation also raises the question of whether hypoglycemia may be a contributor to the observed higher incidence of small-for-gestational-age infants and higher risk of fetal death after bariatric surgery. We recommend that measurements of glucose levels 2 hours after carbohydrate loading (by means of an oral glucose-tolerance test or consumption of a meal) not be used for the diagnosis of gestational diabetes in patients who have undergone gastric bypass surgery. Measurement of fasting blood glucose levels seems to be the best test for the diagnosis in this group, although the appropriate cutoff level requires further research. Continuous glucose monitoring may be of additional value in improving understanding of associations between postprandial hyper- and hypoglycemia and pregnancy outcomes after bariatric surgery. André P. van Beek, M.D., Ph.D. Helen L. Lutgers, M.D., Ph.D. University Medical Center Groningen Groningen, the Netherlands [email protected] No potential conflict of interest relevant to this letter was reported. 1. Kim SH, Liu TC, Abbasi F, et al. Plasma glucose and insulin
regulation is abnormal following gastric bypass surgery with or without neuroglycopenia. Obes Surg 2009;19:1550-6. 2. Itariu BK, Zeyda M, Prager G, Stulnig TM. Insulin-like growth factor 1 predicts post-load hypoglycemia following bariatric surgery: a prospective cohort study. PLoS One 2014;9(4): e94613. 3. Tack J, Arts J, Caenepeel P, De Wulf D, Bisschops R. Pathophysiology, diagnosis and management of postoperative dumping syndrome. Nat Rev Gastroenterol Hepatol 2009;6:583-90. DOI: 10.1056/NEJMc1503863
The Authors Reply: Devlieger et al. raise the possibility that surgical complications may contribute to stillbirth and neonatal death. They cite preliminary data on the incidence of gastric or abdominal symptoms among pregnant women with a history of bariatric surgery. We agree that surgical complications, such as herniation, could contribute to pregnancy complications. However, we could find no support for this hypothesis in our study. By linking data to the Swedish National Patient Register, we identified 16 inpatient admissions during pregnancy of women whose infants either were stillborn or died during the neonatal period. None
of these admissions listed surgery owing to herniation or abdominal pain. Only 1 admission listed a contributory diagnosis code of abdominal pain, and this was because of a tumor. A larger study is needed to properly assess the influence of surgical complications on these mortality rates. Van Beek and Lutgers suggest that measurement of the fasting blood glucose level is the best test for diagnosing gestational diabetes after gastric bypass surgery and should be performed instead of oral glucose-tolerance testing. As we noted in the Methods section of our article, fasting glucose levels and preprandial plus postprandial glucose levels were assessed if oral glucose-tolerance testing was deemed unsafe for patients who had undergone bariatric surgery. We do not know, however, which method was used for diagnosis in individual patients in our study. Without access to the patients’ glucose levels during pregnancy, we cannot investigate whether hypoglycemia could be a hidden determinant of growth restriction and fetal death, as speculated by van Beek and Lutgers. Kari Johansson, Ph.D. Olof Stephansson, M.D., Ph.D. Martin Neovius, Ph.D. Karolinska Institutet Stockholm, Sweden [email protected] Since publication of their article, the authors report no further potential conflict of interest. DOI: 10.1056/NEJMc1503863
The Editorialist Replies: Devlieger et al. explore the potential cause of the difference in perinatal mortality in the bariatric-surgery group in the study by Johansson et al. and in the general Swedish population. Their suggestion that postoperative complications may account for some of the differences is important to remember, but it is equally important to remember that the perinatal mortality rates in the postsurgery group and the control group in the study by Johansson et al. were not significantly different (1.7% and 0.7%, respectively; P = 0.06). Furthermore, it is important to note that the study cited by Devlieger et al. is both ongoing and small at this point and therefore requires a larger sample and peer review. Van Beek and Lutgers remind us to consider carefully the method of diagnostic testing for gestational diabetes in women who have under-
n engl j med 372;23 nejm.org june 4, 2015
2267
The New England Journal of Medicine Downloaded from nejm.org at UC SHARED JOURNAL COLLECTION on June 4, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
The
n e w e ng l a n d j o u r na l
gone bariatric surgery, particularly because of the phenomenon of the dumping syndrome.1 It is true that the dumping syndrome can be seen in women undergoing testing for gestational diabetes. In one recent study, 11 of 19 women (58%) had hypoglycemia in response to the glucose load, which could affect test results.2 Although van Beek and Lutgers discuss the use of fasting glucose levels and continuous glucose monitoring to screen for gestational diabetes, we do not have much guidance for how such tools would be used. In particular, fasting blood glucose levels have been shown to have poor sensitivity for the diagnosis of gestational diabetes.3 The use of self-monitoring of blood glucose levels to diagnose gestational diabetes may be the best approach for women who have had bariatric surgery until we have better data on other methods.4 In the end, these letter writers make the point that we need more research — basic, clinical,
of
m e dic i n e
and translational — to better understand what is underlying the effects of bariatric surgery, particularly in women who are or would like to become pregnant. Aaron B. Caughey, M.D., Ph.D. Oregon Health and Science University Portland, OR Since publication of his article, the author reports no further potential conflict of interest. 1. Tack J, Arts J, Caenepeel P, De Wulf D, Bisschops R. Patho-
physiology, diagnosis and management of postoperative dumping syndrome. Nat Rev Gastroenterol Hepatol 2009;6:583-90. 2. Freitas C, Araújo C, Caldas R, Lopes DS, Nora M, Monteiro MP. Effect of new criteria on the diagnosis of gestational diabetes in women submitted to gastric bypass. Surg Obes Relat Dis 2014;10:1041-6. 3. Anderson V, Ye C, Sermer M, et al. Fasting capillary glucose as a screening test for ruling out gestational diabetes mellitus. J Obstet Gynaecol Can 2013;35:515-22. 4. Allard C, Sahyouni E, Menard J, et al. Gestational diabetes mellitus identification based on self-monitoring of blood glucose. Can J Diabetes 2015;39:162-8. DOI: 10.1056/NEJMc1503863
Ovarian Protection during Adjuvant Chemotherapy To the Editor: In the study by Moore et al. (March 5 issue),1 a statistically significant improvement in disease-free and overall survival was observed in the goserelin group versus the control group, together with a higher number of pregnancies. The authors report that this improvement was “unexpected” and perhaps due to the gonadotropin-releasing hormone (GnRH) receptors on breast-cancer cells. An alternative explanation might be proposed. It has been shown that pregnancy after breast cancer does not decrease survival. In a preplanned analysis conducted in patients with estrogen-receptor–negative breast cancer, the effect of pregnancy was even protective, with a hazard ratio for diseasefree and overall survival of 0.75 and 0.54, respectively.2 Even if the biologic mechanisms of this effect have not been completely elucidated, it is plausible that pregnancy might affect outcomes.3 Thus, the possible confounding effect of pregnancy on survival in the Prevention of Early Menopause Study (POEMS) could be of relevance. Given the small number of pregnancies, it would be interesting to know when they occurred in each group
2268
and if relapses had a different distribution in patients who became pregnant as compared with patients who did not. Fedro A. Peccatori, M.D., Ph.D. European Institute of Oncology Milan, Italy [email protected] No potential conflict of interest relevant to this letter was reported. 1. Moore HCF, Unger JM, Phillips K-A, et al. Goserelin for
ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med 2015;372:923-32. 2. Azim HA Jr, Kroman N, Paesmans M, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol 2013;31:73-9. 3. Azim HA Jr, Santoro L, Pavlidis N, et al. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer 2011;47:74-83. DOI: 10.1056/NEJMc1504241
To the Editor: We have some questions about the use of GnRH analogs to preserve fertility in women with breast cancer who are undergoing chemotherapy. First, when we recalculated the numbers on the basis of patients attempting to
n engl j med 372;23 nejm.org june 4, 2015
The New England Journal of Medicine Downloaded from nejm.org at UC SHARED JOURNAL COLLECTION on June 4, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
n e w e ng l a n d j o u r na l
of
m e dic i n e
pregnant women. The high risk of hepatitis E Jun Zhang, M.Sc. infection for travelers and health care and hu- J. Wai-Kuo Shih, Ph.D. manitarian relief workers who are deployed or Ning-Shao Xia traveling to areas where there is an ongoing Xiamen University School of Public Health China outbreak was also recognized. (It has been re- Xiamen, [email protected] ported that hepatitis E infection was diagnosed Since publication of their article, the authors report no furin health care workers from developed coun- ther potential conflict of interest. tries who had responded to outbreaks in refu- 1. Zhu F-C, Zhang J, Zhang X-F, et al. Efficacy and safety of a gee camps in Africa.3) In the absence of interna- recombinant hepatitis E vaccine in healthy adults: a large-scale, tional guidelines, the reliance on local regulatory randomised, double-blind placebo-controlled, phase 3 trial. Lancet 2010;376:895-902. agencies in outbreak countries that usually have 2. Hepatitis E Vaccine Working Group. Hepatitis E: epidemiology no capacity or experience to conduct qualified and disease burden. Geneva, World Health Organization, 2014 evaluations creates obstacles. In the meantime, (http://www.who.int/immunization/sage/meetings/2014/october/ 1_HEV_burden_paper_final_03_Oct_14_yellow_book.pdf?ua=1). the current manufacturer of the vaccine lacks 3. Hepatitis E vaccine: WHO position paper, May 2015. Wkly the resources to complete registration outside Epidemiol Rec 2015;90(18):185-200. China. One of the possible solutions is to 4. Nelson KE, Shih JW, Zhang J, et al. Hepatitis E vaccine to prevent morbidity and mortality during epidemics. Open Forum develop a ready-to-go preemptive protocol for Infect Dis 2014;1(3):ofu098. future outbreaks.4 DOI: 10.1056/NEJMc1504302
Outcomes of Pregnancy after Bariatric Surgery To the Editor: Johansson et al. (Feb. 26 issue)1 found that pregnancies after bariatric surgery are associated with reduced risks of gestational diabetes and large-for-gestational-age neonates as compared with control pregnancies in obese women. Perinatal mortality, however, was much higher than in the general Swedish population (1.7% vs. 0.4%).2 Both the article and the related editorial3 fail to mention surgical complications as a possible contributing factor. Small-bowel herniations after gastric bypass surgery may result in severe maternal and fetal complications.4 In an ongoing prospective cohort study (www.aurorastudy.org), 9 of 64 pregnant patients (14%) presented with gastric or abdominal symptoms, with 5 (8%) requiring surgery. It is plausible that this contributed to the increased prematurity rate and perinatal mortality in the Swedish cohort. Unfortunately, Johansson and colleagues did not report on obstetrical admissions and surgeries during pregnancy. In pregnant women who had previously undergone bariatric surgery, caregivers should be attentive to symptoms of internal herniation, such as abdominal pain and vomiting, which are often downplayed in pregnancy. Moreover, correct imaging techniques (i.e., computed tomography and magnetic resonance imaging) and operative intervention, which are often performed with reluctance in pregnant women, should not be delayed.5 2266
Roland Devlieger, M.D., Ph.D. Goele Jans, M.Sc. Christophe Matthys, Ph.D. KU Leuven Leuven, Belgium [email protected] No potential conflict of interest relevant to this letter was reported. 1. Johansson K, Cnattingius S, Näslund I, et al. Outcomes of
pregnancy after bariatric surgery. N Engl J Med 2015;372:814-24.
2. Stormdal Bring H, Hulthén Varli IA, Kublickas M, Papadogi-
annakis N, Pettersson K. Causes of stillbirth at different gestational ages in singleton pregnancies. Acta Obstet Gynecol Scand 2014;93:86-92. 3. Caughey AB. Bariatric surgery before pregnancy — is this a solution to a big problem? N Engl J Med 2015;372:877-8. 4. Guelinckx I, Devlieger R, Vansant G. Reproductive outcome after bariatric surgery: a critical review. Hum Reprod Update 2009;15:189-201. 5. Wax JR, Pinette MG, Cartin A. Roux-en-Y gastric bypassassociated bowel obstruction complicating pregnancy — an obstetrician’s map to the clinical minefield. Am J Obstet Gynecol 2013;208:265-71. DOI: 10.1056/NEJMc1503863
To the Editor: Johansson et al. reported important data about pregnancy outcomes after bariatric surgery. A concern is that measurement of 2-hour glucose levels during an oral glucose-tolerance test or after a meal is unsuitable for diagnosing gestational diabetes after gastric bypass surgery. Patients who have undergone this surgery have a very early glucose peak (within 1 hour
n engl j med 372;23 nejm.org june 4, 2015
The New England Journal of Medicine Downloaded from nejm.org at UC SHARED JOURNAL COLLECTION on June 4, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
correspondence
after carbohydrate loading), often followed by hyperinsulinemic hypoglycemia 1 to 3 hours after carbohydrate loading.1-3 This observation also raises the question of whether hypoglycemia may be a contributor to the observed higher incidence of small-for-gestational-age infants and higher risk of fetal death after bariatric surgery. We recommend that measurements of glucose levels 2 hours after carbohydrate loading (by means of an oral glucose-tolerance test or consumption of a meal) not be used for the diagnosis of gestational diabetes in patients who have undergone gastric bypass surgery. Measurement of fasting blood glucose levels seems to be the best test for the diagnosis in this group, although the appropriate cutoff level requires further research. Continuous glucose monitoring may be of additional value in improving understanding of associations between postprandial hyper- and hypoglycemia and pregnancy outcomes after bariatric surgery. André P. van Beek, M.D., Ph.D. Helen L. Lutgers, M.D., Ph.D. University Medical Center Groningen Groningen, the Netherlands [email protected] No potential conflict of interest relevant to this letter was reported. 1. Kim SH, Liu TC, Abbasi F, et al. Plasma glucose and insulin
regulation is abnormal following gastric bypass surgery with or without neuroglycopenia. Obes Surg 2009;19:1550-6. 2. Itariu BK, Zeyda M, Prager G, Stulnig TM. Insulin-like growth factor 1 predicts post-load hypoglycemia following bariatric surgery: a prospective cohort study. PLoS One 2014;9(4): e94613. 3. Tack J, Arts J, Caenepeel P, De Wulf D, Bisschops R. Pathophysiology, diagnosis and management of postoperative dumping syndrome. Nat Rev Gastroenterol Hepatol 2009;6:583-90. DOI: 10.1056/NEJMc1503863
The Authors Reply: Devlieger et al. raise the possibility that surgical complications may contribute to stillbirth and neonatal death. They cite preliminary data on the incidence of gastric or abdominal symptoms among pregnant women with a history of bariatric surgery. We agree that surgical complications, such as herniation, could contribute to pregnancy complications. However, we could find no support for this hypothesis in our study. By linking data to the Swedish National Patient Register, we identified 16 inpatient admissions during pregnancy of women whose infants either were stillborn or died during the neonatal period. None
of these admissions listed surgery owing to herniation or abdominal pain. Only 1 admission listed a contributory diagnosis code of abdominal pain, and this was because of a tumor. A larger study is needed to properly assess the influence of surgical complications on these mortality rates. Van Beek and Lutgers suggest that measurement of the fasting blood glucose level is the best test for diagnosing gestational diabetes after gastric bypass surgery and should be performed instead of oral glucose-tolerance testing. As we noted in the Methods section of our article, fasting glucose levels and preprandial plus postprandial glucose levels were assessed if oral glucose-tolerance testing was deemed unsafe for patients who had undergone bariatric surgery. We do not know, however, which method was used for diagnosis in individual patients in our study. Without access to the patients’ glucose levels during pregnancy, we cannot investigate whether hypoglycemia could be a hidden determinant of growth restriction and fetal death, as speculated by van Beek and Lutgers. Kari Johansson, Ph.D. Olof Stephansson, M.D., Ph.D. Martin Neovius, Ph.D. Karolinska Institutet Stockholm, Sweden [email protected] Since publication of their article, the authors report no further potential conflict of interest. DOI: 10.1056/NEJMc1503863
The Editorialist Replies: Devlieger et al. explore the potential cause of the difference in perinatal mortality in the bariatric-surgery group in the study by Johansson et al. and in the general Swedish population. Their suggestion that postoperative complications may account for some of the differences is important to remember, but it is equally important to remember that the perinatal mortality rates in the postsurgery group and the control group in the study by Johansson et al. were not significantly different (1.7% and 0.7%, respectively; P = 0.06). Furthermore, it is important to note that the study cited by Devlieger et al. is both ongoing and small at this point and therefore requires a larger sample and peer review. Van Beek and Lutgers remind us to consider carefully the method of diagnostic testing for gestational diabetes in women who have under-
n engl j med 372;23 nejm.org june 4, 2015
2267
The New England Journal of Medicine Downloaded from nejm.org at UC SHARED JOURNAL COLLECTION on June 4, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
The
n e w e ng l a n d j o u r na l
gone bariatric surgery, particularly because of the phenomenon of the dumping syndrome.1 It is true that the dumping syndrome can be seen in women undergoing testing for gestational diabetes. In one recent study, 11 of 19 women (58%) had hypoglycemia in response to the glucose load, which could affect test results.2 Although van Beek and Lutgers discuss the use of fasting glucose levels and continuous glucose monitoring to screen for gestational diabetes, we do not have much guidance for how such tools would be used. In particular, fasting blood glucose levels have been shown to have poor sensitivity for the diagnosis of gestational diabetes.3 The use of self-monitoring of blood glucose levels to diagnose gestational diabetes may be the best approach for women who have had bariatric surgery until we have better data on other methods.4 In the end, these letter writers make the point that we need more research — basic, clinical,
of
m e dic i n e
and translational — to better understand what is underlying the effects of bariatric surgery, particularly in women who are or would like to become pregnant. Aaron B. Caughey, M.D., Ph.D. Oregon Health and Science University Portland, OR Since publication of his article, the author reports no further potential conflict of interest. 1. Tack J, Arts J, Caenepeel P, De Wulf D, Bisschops R. Patho-
physiology, diagnosis and management of postoperative dumping syndrome. Nat Rev Gastroenterol Hepatol 2009;6:583-90. 2. Freitas C, Araújo C, Caldas R, Lopes DS, Nora M, Monteiro MP. Effect of new criteria on the diagnosis of gestational diabetes in women submitted to gastric bypass. Surg Obes Relat Dis 2014;10:1041-6. 3. Anderson V, Ye C, Sermer M, et al. Fasting capillary glucose as a screening test for ruling out gestational diabetes mellitus. J Obstet Gynaecol Can 2013;35:515-22. 4. Allard C, Sahyouni E, Menard J, et al. Gestational diabetes mellitus identification based on self-monitoring of blood glucose. Can J Diabetes 2015;39:162-8. DOI: 10.1056/NEJMc1503863
Ovarian Protection during Adjuvant Chemotherapy To the Editor: In the study by Moore et al. (March 5 issue),1 a statistically significant improvement in disease-free and overall survival was observed in the goserelin group versus the control group, together with a higher number of pregnancies. The authors report that this improvement was “unexpected” and perhaps due to the gonadotropin-releasing hormone (GnRH) receptors on breast-cancer cells. An alternative explanation might be proposed. It has been shown that pregnancy after breast cancer does not decrease survival. In a preplanned analysis conducted in patients with estrogen-receptor–negative breast cancer, the effect of pregnancy was even protective, with a hazard ratio for diseasefree and overall survival of 0.75 and 0.54, respectively.2 Even if the biologic mechanisms of this effect have not been completely elucidated, it is plausible that pregnancy might affect outcomes.3 Thus, the possible confounding effect of pregnancy on survival in the Prevention of Early Menopause Study (POEMS) could be of relevance. Given the small number of pregnancies, it would be interesting to know when they occurred in each group
2268
and if relapses had a different distribution in patients who became pregnant as compared with patients who did not. Fedro A. Peccatori, M.D., Ph.D. European Institute of Oncology Milan, Italy [email protected] No potential conflict of interest relevant to this letter was reported. 1. Moore HCF, Unger JM, Phillips K-A, et al. Goserelin for
ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med 2015;372:923-32. 2. Azim HA Jr, Kroman N, Paesmans M, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol 2013;31:73-9. 3. Azim HA Jr, Santoro L, Pavlidis N, et al. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer 2011;47:74-83. DOI: 10.1056/NEJMc1504241
To the Editor: We have some questions about the use of GnRH analogs to preserve fertility in women with breast cancer who are undergoing chemotherapy. First, when we recalculated the numbers on the basis of patients attempting to
n engl j med 372;23 nejm.org june 4, 2015
The New England Journal of Medicine Downloaded from nejm.org at UC SHARED JOURNAL COLLECTION on June 4, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved.
