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Pregnancy in breast cancer survivors: A need for proper counseling
The Breast 18 (2009) 337–338
Contents lists available at ScienceDirect
The Breast journal homepage: www.elsevier.com/brst
Editorial
Pregnancy in breast cancer survivors: A need for proper counseling
Breast cancer is the most common malignant tumor affecting women during their childbearing period, with 12.4% of all cases occurring in women between the age of 20 and 44 years.1 Early detection and more effective adjuvant treatment have significantly decreased breast cancer related mortality, with 2.9 million breast cancer survivors predicted in 2010 in the US.2 Consequently, we are now paying more attention to specific concerns and needs of young patients with breast cancer, including fertility and pregnancy issues.3 While it was thought that a pregnancy following a breast cancer diagnosis would increase the risk of breast cancer relapse by means of hormonal stimulation, several case-control studies have clearly shown that women who got pregnant after an appropriate treatment for their breast cancer, survive similar or even longer compared to non-pregnant breast cancer controls.4,5 Healthy mother effect phenomenon might be a reason6; however, alternative immunological and endocrinal theories have been proposed. Fetal antigens are expressed on breast tumor cells and thus pregnancy would act as a sort of tumor vaccination.7 Moreover, the high estrogen levels during pregnancy might lead to apoptosis of estrogen and progesterone receptors positive breast cancer cells,8 and subsequent estrogen deprivation by means of breast-feeding was found to be associated with better prognosis as well.9 Thus, it is obvious that subsequent pregnancy in breast cancer survivors is not detrimental and might even be protective. In this issue of ‘‘The Breast’’, Rippy et al. report the results of a questionnaire, administered to young breast cancer survivors, addressing pregnancy and fertility issues and the need for reproductive counseling of these patients.10 Authors showed that 36/164 (22%) breast cancer patients wanted to become pregnant before diagnosis, while 24 women were still interested in having children after ending adjuvant therapy. The main reason for not trying to get pregnant was ‘‘completed family’’ (72%). Other reasons included fear of recurrence, fertility and sexual issues. Out of 24 women who wanted to become pregnant, 18 succeeded (75%) with four women getting pregnant more than once. All except 3 were exposed to adjuvant chemotherapy. This is particularly important as it shows that the infertility rate following modern chemotherapy regimens (i.e. anthracycline-based and taxanes) appears low. The majority of these patients underwent a fertility preservation procedure, mostly with LHRH analogue administration during chemotherapy, however it is unknown whether this contributed in the high pregnancy rate. Notably, 3/18 patients had assisted reproduction techniques for
0960-9776/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.breast.2009.09.014
conception, reflecting the rapidly growing successes of this field also for oncological patients. Authors should be commended for their work, even if there are some flaws that should be taken in consideration. Tumor characteristics and demographics of the 164 patients who completed the questionnaire are not clearly understandable, and survival data do not have a reference group well matched for age and known prognostic factors. Moreover, it would have added to the work the information about tumor receptor status and breast feeding attitude of the pregnant patients. However, this information lacks from nearly all the previously reported case-control studies as well. This paper reinforces the need for proper reproductive counseling for young breast cancer patients, which probably contributed to the high success rate of pregnancy in this cohort. It also calls for establishing a reliable way to preserve their fertility. Recently Azim and colleagues have shown that ovarian stimulation with gonadotrophins and letrozole allowed an average harvest of 10 oocytes without increasing breast cancer recurrence risk.11 However, this series was small (79 patients), not randomized and with a short follow-up period (<3 years). The addition of LHRH agonist during the period of chemotherapy is used by some to preserve the ovarian function; however we still lack strong evidence to promote this approach. Currently several large randomized prospective studies are ongoing to answer this question and their results are eagerly awaited. In conclusion, pregnancy after breast cancer should not be discouraged. More research on fertility and pregnancy issues is needed for better defining patients and survivors needs: an extraordinary challenge for all health care providers.
References 1. SEER cancer statistics review. Bethesda: NCI, http://seer.cancer.gov/stactfacts/ html/breast.html; 1975–2006. 2. De Angelis R, Tavilla A, Verdecchia A, et al. Breast cancer survivors in the United States: geographic variability and time trends, 2005–2015. Cancer 2009;115: 1954–66. 3. Surbone A, Peccatori FA. Unmet needs of cancer survivors: supportive care’s new challenge. Support Care Cancer 2006;14:397–9. 4. Peccatori FA, Azim Jr HA. Safety of pregnancy following breast cancer diagnosis. Acta Oncol 2009;48:470–1. 5. Peccatori F, Cinieri S, Orlando L, Bellettini G. Subsequent pregnancy after breast cancer. Recent Results Cancer Res 2008;178:57–67. 6. Sankila R, Heiavaara S, Hakulinen T. Survival of breast cancer patients after subsequent term pregnancy: ‘‘Healthy mother effect’’ Am J Obstet Gynecol 1994;170:818–23. 7. Janerich DT. The fetal antigen hypothesis: cancer and beyond. Med Hypotheses 2001;56:101–3.
338
Editorial / The Breast 18 (2009) 337–338
8. Gizman RC, Yang J, Rajkumar L, Thordarson G, Chen X, Nandi S. Hormonal prevention of breast cancer mimicking the protective effect of pregnancy. Proc Natl Acad Sci USA 1999;96:2520–5. 9. Azim Jr HA, Bellettini G, Gelber S, Peccatori FA. Breast-feeding after breast cancer: if you wish, madam. Breast Cancer Res Treat 2009;114: 7–12. 10. Rippy EE, Karat IF, Kissin MW. Pregnancy after breast cancer: the importance of active counseling and planning. Breast; 2009. xx. 11. Azim AA, Costantini-Ferrando M, Oktay K. Safety of fertility preservation by ovarian stimulation with letrozole and gonadotrophins in patients with breast cancer: a prospective controlled study. J Clin Oncol 2008;26: 2630–5.
Fedro A. Peccatori* Department of Medicine, Division of Oncology/Hematology, European Institute of Oncology, Via Ripamonti 435, Milan 20141, Italy Corresponding author. Tel.: þ390257489538; fax: þ390294379241. E-mail address: [email protected] Hatem A. Azim Jr. Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
Contents lists available at ScienceDirect
The Breast journal homepage: www.elsevier.com/brst
Editorial
Pregnancy in breast cancer survivors: A need for proper counseling
Breast cancer is the most common malignant tumor affecting women during their childbearing period, with 12.4% of all cases occurring in women between the age of 20 and 44 years.1 Early detection and more effective adjuvant treatment have significantly decreased breast cancer related mortality, with 2.9 million breast cancer survivors predicted in 2010 in the US.2 Consequently, we are now paying more attention to specific concerns and needs of young patients with breast cancer, including fertility and pregnancy issues.3 While it was thought that a pregnancy following a breast cancer diagnosis would increase the risk of breast cancer relapse by means of hormonal stimulation, several case-control studies have clearly shown that women who got pregnant after an appropriate treatment for their breast cancer, survive similar or even longer compared to non-pregnant breast cancer controls.4,5 Healthy mother effect phenomenon might be a reason6; however, alternative immunological and endocrinal theories have been proposed. Fetal antigens are expressed on breast tumor cells and thus pregnancy would act as a sort of tumor vaccination.7 Moreover, the high estrogen levels during pregnancy might lead to apoptosis of estrogen and progesterone receptors positive breast cancer cells,8 and subsequent estrogen deprivation by means of breast-feeding was found to be associated with better prognosis as well.9 Thus, it is obvious that subsequent pregnancy in breast cancer survivors is not detrimental and might even be protective. In this issue of ‘‘The Breast’’, Rippy et al. report the results of a questionnaire, administered to young breast cancer survivors, addressing pregnancy and fertility issues and the need for reproductive counseling of these patients.10 Authors showed that 36/164 (22%) breast cancer patients wanted to become pregnant before diagnosis, while 24 women were still interested in having children after ending adjuvant therapy. The main reason for not trying to get pregnant was ‘‘completed family’’ (72%). Other reasons included fear of recurrence, fertility and sexual issues. Out of 24 women who wanted to become pregnant, 18 succeeded (75%) with four women getting pregnant more than once. All except 3 were exposed to adjuvant chemotherapy. This is particularly important as it shows that the infertility rate following modern chemotherapy regimens (i.e. anthracycline-based and taxanes) appears low. The majority of these patients underwent a fertility preservation procedure, mostly with LHRH analogue administration during chemotherapy, however it is unknown whether this contributed in the high pregnancy rate. Notably, 3/18 patients had assisted reproduction techniques for
0960-9776/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.breast.2009.09.014
conception, reflecting the rapidly growing successes of this field also for oncological patients. Authors should be commended for their work, even if there are some flaws that should be taken in consideration. Tumor characteristics and demographics of the 164 patients who completed the questionnaire are not clearly understandable, and survival data do not have a reference group well matched for age and known prognostic factors. Moreover, it would have added to the work the information about tumor receptor status and breast feeding attitude of the pregnant patients. However, this information lacks from nearly all the previously reported case-control studies as well. This paper reinforces the need for proper reproductive counseling for young breast cancer patients, which probably contributed to the high success rate of pregnancy in this cohort. It also calls for establishing a reliable way to preserve their fertility. Recently Azim and colleagues have shown that ovarian stimulation with gonadotrophins and letrozole allowed an average harvest of 10 oocytes without increasing breast cancer recurrence risk.11 However, this series was small (79 patients), not randomized and with a short follow-up period (<3 years). The addition of LHRH agonist during the period of chemotherapy is used by some to preserve the ovarian function; however we still lack strong evidence to promote this approach. Currently several large randomized prospective studies are ongoing to answer this question and their results are eagerly awaited. In conclusion, pregnancy after breast cancer should not be discouraged. More research on fertility and pregnancy issues is needed for better defining patients and survivors needs: an extraordinary challenge for all health care providers.
References 1. SEER cancer statistics review. Bethesda: NCI, http://seer.cancer.gov/stactfacts/ html/breast.html; 1975–2006. 2. De Angelis R, Tavilla A, Verdecchia A, et al. Breast cancer survivors in the United States: geographic variability and time trends, 2005–2015. Cancer 2009;115: 1954–66. 3. Surbone A, Peccatori FA. Unmet needs of cancer survivors: supportive care’s new challenge. Support Care Cancer 2006;14:397–9. 4. Peccatori FA, Azim Jr HA. Safety of pregnancy following breast cancer diagnosis. Acta Oncol 2009;48:470–1. 5. Peccatori F, Cinieri S, Orlando L, Bellettini G. Subsequent pregnancy after breast cancer. Recent Results Cancer Res 2008;178:57–67. 6. Sankila R, Heiavaara S, Hakulinen T. Survival of breast cancer patients after subsequent term pregnancy: ‘‘Healthy mother effect’’ Am J Obstet Gynecol 1994;170:818–23. 7. Janerich DT. The fetal antigen hypothesis: cancer and beyond. Med Hypotheses 2001;56:101–3.
338
Editorial / The Breast 18 (2009) 337–338
8. Gizman RC, Yang J, Rajkumar L, Thordarson G, Chen X, Nandi S. Hormonal prevention of breast cancer mimicking the protective effect of pregnancy. Proc Natl Acad Sci USA 1999;96:2520–5. 9. Azim Jr HA, Bellettini G, Gelber S, Peccatori FA. Breast-feeding after breast cancer: if you wish, madam. Breast Cancer Res Treat 2009;114: 7–12. 10. Rippy EE, Karat IF, Kissin MW. Pregnancy after breast cancer: the importance of active counseling and planning. Breast; 2009. xx. 11. Azim AA, Costantini-Ferrando M, Oktay K. Safety of fertility preservation by ovarian stimulation with letrozole and gonadotrophins in patients with breast cancer: a prospective controlled study. J Clin Oncol 2008;26: 2630–5.
Fedro A. Peccatori* Department of Medicine, Division of Oncology/Hematology, European Institute of Oncology, Via Ripamonti 435, Milan 20141, Italy Corresponding author. Tel.: þ390257489538; fax: þ390294379241. E-mail address: [email protected] Hatem A. Azim Jr. Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt