Cancer in pregnancy


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Cancer in pregnancy

  1. 1. ORIGINAL ARTICLE Khalid H. Sait Æ Adnan Ashour Æ Mohammad Rajabi Pregnancy outcome in non-gynecologic cancer Received: 13 December 2003 / Accepted: 8 March 2004 / Published online: 2 June 2004 Ó Springer-Verlag 2004 Abstract Objective: The objective was to determine the prevalence of non-gynecologic cancer in pregnancy and its maternal and fetal outcome in a single tertiary center in the Eastern Province of Saudi Arabia. Method: Ret- rospective chart review was done of 54 patients with a diagnosis of non-gynecologic cancer in pregnancy at Dhahran Health Center from January 1990 to December 2001 using the Dhahran Health Information database. Maternal and fetal outcome were determined for 17 women with active cancer during pregnancy (Group I, 18 pregnancies) and for 44 women in cancer remission (Group II, 96 pregnancies). Seven women were pregnant during active cancer and during cancer remission. Results: There were 114 pregnancies in 54 women with cancer. The prevalence in pregnancy was 1.5:1,000 (54 cancer in 70,987 pregnancies). Thyroid (33) and breast (11) cancer accounted for 75% of all cancer. Induced abortion, spontaneous abortion, stillbirth and low birth weights in Group I were: 5 (28%), 0 (0%), 1 (6%) and 2 (11%), respectively, and in Group II were: 1 (1%), 11 (11%), 0 (0%) and 3 (3%), respectively. Live births for Group I, II and all patients with cancer were 12 (66.7%), 84 (87.5%) and 96 (84.2%), respectively, with p =0.025 There were three maternity deaths among 17 women in Group I. None of 44 women in Group II died. Conclu- sion: The diagnosis of active cancer in pregnancy carries a significant increase in perinatal and maternal mortal- ity. However, pregnancy during cancer in remission has favorable outcome, pregnancy in this group should not be discouraged. Keywords Cancer in pregnancy Æ Prevalence Æ Outcome Introduction Cancer is a major cause of death in women in the reproductive age. Approximately 1:6,000 women will be affected by cancer while pregnant. The most frequent non-gynecologic malignancies in reproductive age group are lymphoma, thyroid cancer, breast cancer and malignant melanoma [1]. Although reviews on preg- nancy outcome in cancer patients have been encouraging [1, 2], only a small percentage of women get pregnant after treatment. About 10% of women treated for breast cancer become pregnant [3, 4]. This may be due to an increase in infertility secondary to chemotherapy and radiation therapy [5]. The contributions of patient’s fear from getting pregnant and possible discouragement by health care providers to the low pregnancy rate are un- known. The objective of this study is to determine pregnancy outcome in women with non-gynecologic malignancy in a tertiary referral center in the Eastern Province of Saudi Arabia. Methods A retrospective study of pregnant women with the diagnosis, or history of, non-gynecologic cancer was done at Dhahran Health Center, from January 1990 to December 2001 using Dhahran Health Information database. Medical records were reviewed and the following data were obtained and entered into study database: type of cancer and its treatment, date and age at diagnosis and the number of pregnancies during and after cancer diagnosis and treatment. Maternal and fetal outcome were also determined. Outcome of pregnancy was classified as live birth, spontaneous abortion, induced abortion, stillbirth, low birth weight (<2,500 g) and birth defects. Women were divided into two groups. Group I: patients with active non-gynecologic cancer during pregnancy. Group II: patients in cancer remission during pregnancy. Data were collected and entered into Excel for analysis. Statistical K. H. Sait (&) Departments of Obstetrics and Gynecology, King Abdulaziz University Hospital, P.O. Box 80215, 21589 Jeddah, Saudi Arabia E-mail: Tel.: +966-2-6408293 Fax: +966-2-6408316 A. Ashour Æ M. Rajabi Departments of Obstetrics and Gynecology, Dhahran Health Center, Saudi Aramco, Dhahran, Saudi Arabia Arch Gynecol Obstet (2005) 271: 346–349 DOI 10.1007/s00404-004-0627-9
  2. 2. analysis was performed using the SPS statistics program and chi- square tests (Statistical significance is defined as p<0.05). Results During the 12-year study period, 114 pregnancies in 54 women with non-gynecologic cancer were found with a prevalence of 1.5 per 1,000 (1 per 623) pregnancies. The mean pregnancy per woman was two with a range of 1– 7. The mean age and (range) in years at diagnosis for thyroid, breast and all cancers were 30 (22–41), 28 (22– 41) and 33 (25–41), respectively. Thyroid cancer (30) and breast cancer (11) accounted for 75% of all non-gyne- cologic cancer that was diagnosed in pregnant women (Table 1). Out of 114 pregnancies, 18 (15.7%) occurred in women with active cancer and 96 (84.2%) occurred in women in cancer remission. Eighteen pregnancies occurred in 17 women in Group I. Fifteen were newly diagnosed cancer at a mean gestational age of 15 weeks (4–33 weeks). Five women had elective termination of pregnancy at gestational ages between 5 and 15 weeks; 3 with breast cancer and 2 with thyroid cancer. Ten women elected to continue the pregnancy, 9 fetuses survived and 3 women died. One woman had fetal distress in labor, she refused Cesarean section, baby died in utero and she died 2 days later from stomach cancer metastasis. Two women in Group I had three pregnancies during chemotherapy treatment who continued pregnancy. One had normal live birth after chemotherapy treatment for acute myelocytic leu- kemia at 18 weeks’ gestation and the other woman had two live births on tamoxifen for breast cancer. This patient died 2 months after her second delivery. The third maternal death was a patient who died 3 months after delivery of normal baby from breast cancer metastasis. In Group I, the numbers and (rates) of live birth, spontaneous abortion, elective pregnancy termi- nation and stillbirth were 12 (66.7%), 0 (0%), 5(27.8%) and 1 (5.6%), respectively (Table 2). Ninety-six pregnancies occurred in 44 women in Group II. Thyroid and breast cancer were present in 69 (71.9%) and 9 (9.4%) of pregnancies, respectively (Table 1). None of these patients died. The numbers and (rates) of live birth, spontaneous abortion, elective pregnancy termination and stillbirth were 84 (87.5%), 11 (11.5%), 1 (1%) and 0 (0%), respectively (Table 3). There were three babies with low birth weight and one baby with osteogenesis imperfecta. Seven women in this study were pregnant during active cancer and during cancer remission. Live birth for all patients with cancer was 84.2% (96 out of 114 pregnancies). Live birth for Group I and Group II were 66.7% (12 out of 18 pregnancies) and 87.5% (84 out of 96 pregnancies), respectively. This dif- ference was statistically significant (Chi-square; p=0.025; Table 2). There were 18 abnormal pregnancy outcome in 108 pregnancies (excluding six elective terminations in Group I and II; Table 3). Abnormal pregnancy outcome occurred in 23.1% (3 out of 13) and 15.8% (15 out of 95) in Groups I and II, respectively. The difference is statis- tically not significant (p=0.508). Discussion This is the largest series of pregnancy in non-gynecologic cancer patients from a single institution. The prevalence of cancer during pregnancy in our population is 1.5 in 1,000 (1 per 623) pregnancies. This figure is much higher than previously published reports in other regions that was reported at 1 in 6,000 pregnancies [1]. Eighty-four percent of our patients were in cancer remission during pregnancy. Although active cancer was present in only 1 in 6 women during pregnancy (16%), it accounted for all the three maternal deaths and over 80% of therapeutic termination of pregnancy. With a comprehensive mul- tidisciplinary medical care provided by maternal-fetal medicine specialists, oncologists and neonatologists, two thirds of women with active cancer during pregnancy Table 1 Pregnancies in women with cancer Cancer types Women (%) Group I active cancer (%) Group II remission (%) Total pregnancies (%) Thyroid 30 (55.6) 8 69 77 (67.6) Breast 11 (20.4) 7 9 16 (14) Hematological 5 (9.3) 1 7 8 (7) Melanoma 2 (3.7) – 2 2 (1.8) Other 6 (11) 2 9 11 (9.6) All cancer 54 18 (15.7) 96 (84.2) 114 (100) Table 2 Outcome of pregnancies in women with cancer Group Women Pregnancies Live birth (%) Spontaneous abortion (%) Elective abortion (%) Stillbirth (%) I Active cancer 17 18 12b (66.7) 0 (0) 5 (27.8) 1 (5.6) II Cancer remission 44 96 84c (87.5) 11 (11.5) 1 (1) 0 (0) Total 54a 114 96 (84.2) 11 (9.6) 6 (5.3) 1 (0.9) a Seven women included in the two groups (were pregnant during active cancer and then pregnant again when cancer in remission) b Include two babies with low birth weight c Include three babies with low birth weight and one baby with osteogenesis imperfecta 347
  3. 3. and 87.5% of women in cancer remission had live newborns. Excluding women who did not abort during the first trimester of pregnancy, 80% of women with active cancer and all women in cancer remission had live newborns. Onset of malignancy during pregnancy is distressing for the future parents and raises thorny problems for the oncologists, obstetrics and gynecologists and neo- natologist. Although active cancer during pregnancy is infrequent, its management is difficult for the patients, family and their physicians. When a woman with can- cer or a history of cancer becomes pregnant a favorable outcome is especially uncertain, in part because some antineoplastic agents are known human teratogens [6– 8]. With rare exceptions, reports of pregnancy outcome in women with cancer are few and inconclusive espe- cially with non-gynecological malignancies [9, 10]. Cancer of thyroid was the most common cancer in this study (77 pregnancies in 30 patients). Subsequent pregnancy after treatment with 131 I appears to be safe. Impairment of gonadal function by iodine is temporary and reversible. There does not seem to be an increased incidence of adverse pregnancy outcome [11, 12]. It is recommended to avoid conception for 1 year after iodine treatment to ensure complete elimination of the radionuclide [12]. In this study, 14% (11 of 77) preg- nancies with thyroid cancer in remission had an abnormal pregnancy outcome (spontaneous abortion = 8 and LBW = 3). Six of these 11 patients received postoperative131 I. Abnormal pregnancy outcome (18 pregnancies in 15 patients) and the type of cancer is presented in Table 3. A review of the recent English literature on cancer in pregnancy including this study is presented in Table 4. There were a total of 562 preg- nancies in 424 women with cancer. The overall live birth, low birth weight, stillbirth, birth defects, spon- taneous abortion and therapeutic abortion were 73.3, 10.3, 4.8, 3.8, 8 and 10.9%, respectively. The overall pregnancy outcome in our study population compared favorably with previously published studies [13–18] (Table 4). Women in cancer remission who remain cancer free during pregnancy are expected to have favorable pregnancy outcome. Women in active cancer during pregnancy also carry a significant mortality risk. One in six women with active non-gynecologic cancer in this study died during pregnancy or in the immediate postpartum period from cancer metastasis. The bright side to the devastating diagnosis of active cancer in pregnancy is the finding that 4 out of 5 women who elected to continue the pregnancy did have live new- borns. The authors emphasis that in preconception counseling of women with cancer the couple should be informed about the possible effect of pregnancy on cancer recurrent and survival especially the estrogen dependent cancer, i.e., breast cancer which were not addressed in this study and remain to be determined. The overall incidence of birth defects of 3.8% is not significantly higher than the 3% incidence reported in the general population [6]. In conclusion, the diagnosis of active cancer in pregnancy carries a significance increase in perinatal and maternal mortality. However, pregnancy during cancer remission has a favorable outcome; pregnancy in this group should not be discouraged. The obstetrician, in close collaboration with the oncologist has a major role in choosing the most appropriate diagnostic and thera- peutic strategy and must keep the couple fully informed. Cancer in pregnancy requires careful consideration of multiple complex issues to achieve the most favorable outcome for mother and fetus. Table 3 Abnormal pregnancies outcome in cancer women. Group I consisted of women with active cancer, Group II of women in cancer remission Abnormal outcome Cancer type Treatment Group Age (years) Gestational age (weeks) Outcome Comment 1 Stomach cancer Patient refused therapy I 29 29 Stillbirth Refused cesarean, died postpartum 2 AML Chemotherapy II 40 41 Spontaneous abortion – 3 and 4a Breast cancer Surgery, refused chemotherapy I 40 40, 41 Low birth weight · 2 Tamoxifen, died postpartum 5 Breast cancer Surgery and chemotherapy II 34 39 Spontaneous abortion – 6 Hodgkin’s lymphoma Surgery and chemotherapy II 29 31 Spontaneous abortion Normal birth · 1 7 Melanoma Surgery II 20 26 Birth defect Osteogenesis imperfecta 8 Thyroid Surgery II 22 24 Spontaneous abortion Normal birth · 5 9 Thyroid Surgery II 30 31 Spontaneous abortion Normal birth · 1 10 Thyroid Surgery II 23 25 Spontaneous abortion – 11 and 12a Thyroid Surgery II 35 36, 37 Spontaneous abortion · 2 Normal birth · 1 13 Thyroid Surgery and iodine therapy II 30 32 Spontaneous abortion Normal birth · 3 14 Thyroid Surgery and iodine therapy II 32 36 Low birth weight Normal birth · 2 15 Thyroid Surgery and iodine therapy II 22 30 Spontaneous abortion – 16 and 17a Thyroid Surgery and iodine therapy II 22 24, 26 Low birth weight · 2 – 18 Thyroid Surgery and iodine therapy II 23 26 Spontaneous abortion – a Women with active cancer and in remission 348
  4. 4. Acknowledgments The authors acknowledge the use of Saudi Aramco Medical Services Organization (SAMSO) facilities for the research data utilized in this manuscript. Opinions expressed in this article are those of the authors and not necessarily of SAMSO. References 1. Cunningham FG, Gant NF, Levano KJ, Gilstrap LC III, Hauth JC, Wenstrom KD (2001) Neoplastic diseases. Williams obstetrics, 21st edn. McGraw-Hill, New York, pp 1439–1459 2. Antonelli NM, Dotters DJ, Katz VL, Kuller JA (1996) Cancer in pregnancy: overview of the literature. Obstet Gynecol Surv 51:125–142 3. Harvey JC, Rosen PP, Ashikari R, Robbins GF, Kinne DW (1981) The effect of pregnancy on the prognosis of carcinoma of the breast following radical mastectomy. Surg Gynecol Obstet 153:723–725 4. Hornstein E, Skornick Y, Rozin R (1982) The management of breast carcinoma in pregnancy and lactation. J Surg Oncol 21:179–182 5. Gradishar WJ, Schilsky RL (1989) Ovarian function following radiation and chemotherapy for cancer. Semin Oncol 16:425– 436 6. Cunningham FG, Gant NF, Levano KJ, Gilstrap LC III, Hauth JC, Wenstrom KD (2001) Teratology, drugs and med- ications. Williams obstetrics, 21st edn. McGraw-Hill, New York, pp 1005–1038 7. Shapard TH (1986) Catalog of teratogenic agents, 5th edn. John’s Hopkins, Baltimore, p 121 8. Sieber SM, Adamson RH (1975) Toxicity of antineoplastic agents in man, chromosomal aberrations antifertility effects, congenital malformations, and carcinogenic potential. Adv Cancer Res 22:57–155 9. Holmes GE, Holmes FF (1978) Pregnancy outcome of patients treated for Hodgkin’s disease: a controlled study. Cancer 41:1317–1322 10. Blatt J, Mulvihill JJ, Ziegler JL, Young RC, Poplack DG (1980) Pregnancy outcome following cancer chemotherapy. Am J Med 69:828–832 11. Schlumberger M, De Vathaire F, Ceccaelli C, Francese C, Pinchera C, Parmentier C (1995) Outcome of pregnancy in women with thyroid carcinoma. J Endocrinol Invest 18: 150–151 12. Casara D, Rubello D, Saladini G, Piotto A, Pelizzo MR, Girelli ME (1993) Pregnancy after high therapeutic doses of iodine- 131 in differentiated thyroid cancer: potential risk and recom- mendations. Eur J Nucl Med 20:192–194 13. Mulvihill JJ, McKeen EA, Rosner F, Zarrabi MH (1987) Pregnancy outcome in cancer patients. Experience in a large cooperative group. Cancer 60:1143–1150 14. Zuazu J, Julia A, Sierra J, Valentin MG, Coma A, Sanz MA (1991) Pregnancy outcome in hematologic malignancies. Can- cer 67:703–709 15. Reynoso EE, Shepherd FA, Messner HA, Farquharson HA, Garvey MB, Baker MA (1987) Acute leukemia during pregnancy: the Toronto leukemia study group experience with long-term follow-up of children exposed in utero to chemo- therapeutic agents. J Clin Oncol 5:1098–1106 16. Zemlickis D, Lishner M, Degendorfer P, Panzarella T, Burke B, Sutcliffe SB (1992) Maternal and fetal outcome after breast cancer in pregnancy. Am J Obstet Gynecol 166:781–787 17. Lishner M, Zemlickis D, Degendorfer P, Panzarella T, Sutcliffe SB, Koren G (1992) Maternal and fetal outcome following Hodgkin’s disease in pregnancy. Br J Cancer 65:114–117 18. Woods JB, Martin JN, Ingram FH, Odom CD, Scott-Conner CE, Rhodes RS (1992) Pregnancy complicated by carcinoma of the colon above the rectum. Am J Perinatol 9:102–110 Table4Outcomeofpregnancyinwomenwithcancer(Englishliterature) ReferenceTypeofstudyYearCancertypeWomenPregnancyLivebirthLBWSBBirthdefectSATA [13]USAquestionnaire1992Allcancer661339891014418 [14]Spanishquestionnaire1991Hematologic48564322157 [15]Literaturereview1987Leukemia58582842223 [16]Originalresearch1992Breast11811983NA2NA1222 [17]Originalresearch1992Hodgkin485039NA2154 [18]Literaturereview1992Colon323225105NA11 Present study Originalresearch2002Non-gynecologic5411496(84%)5(4.4%)1(0.9%)1(0.9%)11(9.6%)6(5.3%) Total–––424562412/562(73.3%)30/290(10.3%)24/501(4.8%)19/501(3.8%)40/50(18%)61/562(10.9%) 349