Review
Cancer and pregnancy: Poena magna, not anymore

https://doi.org/10.1016/j.ejca.2005.10.014Get rights and content

Abstract

Cancer diagnosed during pregnancy constitutes a difficult clinical condition with a devastating impact on the patient’s somatic and psychosocial health and possibly on foetal integrity. This circumstance also raises several moral, religious, social and familial dilemmas. In this review we critically present available evidence regarding the incidence, epidemiology and genetics of cancer in pregnant women, its presentation, diagnosis and staging as well as therapeutic management. Issues such as maternal/foetal prognosis, need for termination of pregnancy, risk of foetal health injury and necessity of psychosocial support are reviewed. Recent accumulating evidence suggests that, with appropriate management, poena magna should not be used to define neither cancer nor pregnancy.

Introduction

Cancer diagnosed during pregnancy is a dramatic event with profound impact on the lives of the patient, offspring, family and physician. As women in developed societies defer child-bearing to the third or fourth decade of life, this rare association is likely to become more common. Curing the patient should still remain the top priority when this is deemed feasible. The dilemma of continuing pregnancy till birth of a viable foetus may turn out to be a complicated one and medical, social, personal, moral as well as religious factors interact to define the chosen course of action. Thorough evaluation of the patient and foetus, the biology and stage of the tumour and of therapeutic alternatives available are necessary for correct prioritization of goals and rationalization of management. The complex issues arising render this clinical condition extremely demanding for expertise and multidisciplinary care. In this article, data are reviewed and key aspects of epidemiology, diagnosis, management and outcome of pregnant women with cancer and embryos are presented.

Section snippets

Epidemiology and genetics

Cancer association with pregnancy (CAP) is poorly studied epidemiologically. The estimated incidence in developed societies is 1:1000 pregnancies, while it is probably lower in developing nations due to the younger age of pregnant women [1]. CAP is becoming more common over the last thirty years, the main reason being the increasing number of women child-bearing at older age [2]. The incidence of malignant diseases during the reproductive age has not increased over time but is known to be

Diagnostic work-up and radiological imaging

The diagnostic work-up of the pregnant woman with cancer should limit exposure to ionizing radiation and be restricted to procedures that do not endanger foetal health. Physical examination should be thorough with particular emphasis on search for palpable lymph nodes, skin lesions, breast abnormalities, enlarged liver or spleen. Gentle meticulous examination of the abdomen, pelvis and rectum is warranted in several clinical settings. In general, fine needle aspiration and excisional or

Safety of pharmacotherapy of the pregnant patient with cancer

Cytotoxic chemotherapy causes genetic damage in exposed somatic cells, including chromosomal breaks, translocations, deletions, gene mutations, aneuploidy and cell cycle disruption [27]. When administered during pregnancy, considerable concern has been generated by cell culture and animal data regarding the mutagenic, teratogenic and carcinogenetic effects on the developing embryo as well as the induced placental damage. Most cytotoxic drugs have a molecular weight less than 600 KDa, and can

Radiation therapy during pregnancy

The developing human embryo and foetus are extremely sensitive to ionizing radiation, which might cause pregnancy loss, malformations, growth retardation and neurobehavioral defects. Most such anomalies appear at foetal doses in excess of 200 mGy, though avoidance of exposure to doses higher than 100 mGy is advised because of the non-deterministic nature of radiobiological events 19, 24. Radiation doses used in cancer therapy are in the range of 30–70 Gy. However, the effective foetal dose depends

Basic principles of management of the pregnant cancer patient

Accumulating evidence suggests that during the first trimester, when treatment cannot be delayed or is administered, termination of pregnancy is advisable. Still, one must bear in mind that even in cases of uterine exposure to combination chemotherapy during the first gestational trimester, the chances of normal embryonal development are around 75%. Previous studies in leukaemic patients suggested that treatment during the first trimester can be accomplished safely. Therefore, any

Cervical cancer

Cervical cancer is probably the most common CAP of visceral organs. Median age at diagnosis of pregnant women is 30–35. Common presenting symptoms are vaginal bleeding, discharge or rarely, pelvic pain. The majority of women with cervical CAP are asymptomatic, diagnosed by abnormal cytology at early stages of the disease (stages IA–IIA in 80% of CAP cases) [58]. It is not yet known whether this presentation with early cancer is due to the frequent gynaecological examinations during prenatal

Placental and foetal metastases and subsequent pregnancies

Vertical transmission of malignant cells to the placenta or foetus is uncommon. In the most updated literature review in 2003, only 62 cases are included [122]. Placentofoetal malignant seeding takes place via hematogenous spread and less often via lymphatic spread or contiguous invasion (pelvic tumours). The malignant neoplasms more commonly affecting the placenta and foetus are melanomas (32% of reported cases), leukaemias/lymphomas (15%), breast cancer (13%), gastric cancer (3%), lung cancer

Psychosocial support of the pregnant patient and family

As experienced by the future mother, the coexistence of cancer with pregnancy is a dramatic circumstance when two irreconcilable realities: the process of creating life with the process of destroying life, meet. At a time of great joy and hope, comes a devastating blow along with the fear of death. As medical, psychological, religious, social and moral standards tower over them, both patient and physician will struggle to find the right balance that combines maximum patient benefit with minimum

Conflict of interest statement

None declared.

References (130)

  • A.K. Sood et al.

    Paclitaxel and platinum chemotherapy for ovarian carcinoma during pregnancy

    Gynecol Oncol

    (2001)
  • A.M. Gonzalez-Angulo et al.

    Paclitaxel chemotherapy in a pregnant patient with bilateral breast cancer

    Clin Breast Cancer

    (2004)
  • A. Aviles et al.

    Hematological malignancies and pregnancy: a final report of 84 children who received chemotherapy in utero

    Clin Lymphoma

    (2001)
  • D.H. Minsker et al.

    Effects of the biphosphonate, alendronate, on parturition in the rat

    Toxicol Appl Pharmacol

    (1993)
  • T.M. Illidge et al.

    Malignant hypercalcemia in pregnancy and antenatal administration of intravenous pamidronate

    Clin Oncol

    (1996)
  • E.S. Medlock et al.

    Granulocyte-colony stimulating factor crosses the placenta and stimulates foetal rat granulopoiesis

    Blood

    (1993)
  • P.H. Van der Giessen

    Measurement of the peripheral dose for the tangential breast treatment technique with Co-60 gamma radiation and high-energy X-rays

    Radiother Oncol

    (1997)
  • M. Mazonakis et al.

    Radiotherapy of Hodgkin‘s disease in early pregnancy: embryo dose measurements

    Radiother Oncol

    (2003)
  • S.Y. Woo et al.

    Radiotherapy during pregnancy for clinical stages IA–IIA Hodgkin’s disease

    Int J Radiat Oncol Biol Phys

    (1992)
  • E. Fenig et al.

    Pregnancy and radiation

    Cancer Treat Rev

    (2001)
  • E. Paraskevaidis et al.

    Management and evolution of cervical intraepithelial neoplasia during pregnancy and postpartum

    Eur J Obstet Gynecol Reprod Biol

    (2002)
  • A.K. Sood et al.

    Surgical management of cervical cancer complicating pregnancy: a case-control study

    Gynecol Oncol

    (1996)
  • N. Germann et al.

    Management and clinical outcomes of pregnant patients with invasive cervical cancer

    Ann Oncol

    (2005)
  • O. Gentilini et al.

    Safety of sentinel node biopsy in pregnant patients with breast cancer

    Ann Oncol

    (2004)
  • D. Zemlickis et al.

    Maternal and foetal outcome after breast cancer in pregnancy

    Am J Obstet Gynecol

    (1992)
  • R.M. Mackie et al.

    Lack of effect of pregnancy on outcome of melamona: The WHO Melanoma programme

    Lancet

    (1991)
  • J.W. Pennoyer et al.

    Changes in size of melanocytic nevi during pregnancy

    J Am Acad Dermatol

    (1997)
  • D. Peleg et al.

    Lymphoma and leukaemia complicating pregnancy

    Obstet Gynecol Clin North Am

    (1998)
  • G. Ferrandina et al.

    Management of an advanced ovarian cancer at 15 weeks of gestation: case report and literature review

    Gyn Oncol

    (2005)
  • E.C. Grendys et al.

    Ovarian cancer in pregnancy

    Surg Clin North Am

    (1995)
  • P. Mathevet et al.

    Laparoscopic management of adnexal masses in pregnancy: a case series

    Eur J Obstet Gynecol Reprod Biol

    (2003)
  • S. Al Bahar et al.

    Pregnancy in chronic myeloid leukaemia patients treated with alpha-interferon

    Int J Gynaecol Obstet

    (2004)
  • N.A. Pavlidis

    Coexistence of pregnancy and malignancy

    The Oncologist

    (2002)
  • N.M. Antonelli et al.

    Cancer in pregnancy: a review of the literature. Part I–II

    Obstet Gynecol Surv

    (1996)
  • A. Jemal et al.

    Cancer statistics 2003

    CA Cancer J Clin

    (2003)
  • J. Nevin et al.

    Cervical carcinoma associated with pregnancy

    Obstet Gynecol Surv

    (1995)
  • L.H. Smith et al.

    Obstetrical deliveries associated with maternal malignancy in California, 1992 through 1997

    Am J Obstet Gynecol

    (2001)
  • O. Johansson et al.

    Pregnancy-associated breast cancer in BRCA1 and BRCA2 germ-line mutation carriers

    Lancet

    (1998)
  • R.O. Dillman et al.

    Malignant melanoma and pregnancy ten questions

    West J Med

    (1996)
  • C.M. Grin et al.

    Pregnancy and the prognosis of malignant melanoma

    Semin Oncol

    (1996)
  • E. Sadurai et al.

    Hematologic malignancies during pregnancy

    Clin Obstet Gynecol

    (1995)
  • F.T. Ward et al.

    Lymphoma and pregnancy

    Semin Oncol

    (1989)
  • D. Serraino et al.

    Cancer incidence in a cohort of human immunodeficiency virus seroconverters: HIV Italian Seroconversion Study Group

    Cancer

    (1997)
  • M.A. Bernstein et al.

    Colon and rectal cancer in pregnancy

    Dis Colon Rectum

    (1993)
  • Q.S. Ringeberg et al.

    Endocrine tumours and miscellaneous cancers in pregnancy

    Semin Oncol

    (1989)
  • P. Duncan et al.

    Foetal risk of anesthesia and surgery during pregnancy

    Anesthesiology

    (1986)
  • International Commission on Radiological Protection

    Pregnancy and medical irradiation

    Ann ICRP

    (2000)
  • International Commission on Radiological Protection: Biological effects after prenatal irradiation (embryo and foetus)

    ICRP publication 90

    Ann ICRP

    (2003)
  • Y. Bentur

    Prenatal irradiation and cancer

  • UNSCEAR. Sources and effects of ionizing radiation. Annex J, developmental effects of irradiation in utero. New York:...
  • Cited by (0)

    View full text