This Article Abstract Full Text (PDF) An erratum has been published eLetters: Submit a response to this article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pavlidis, N. A. Search for Related Content PubMed PubMed Citation Articles by Pavlidis, N. A.

Coexistence of Pregnancy and Malignancy

Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece

Nicholas A. Pavlidis, M.D., Department of Medical Oncology, Medical School, University of Ioannina, 45110 Greece. Telephone and Fax: 30-651-99394 and 30-651-97505; e-mail: npavlid{at}cc.uoi.gr

	ABSTRACT

Top Abstract Introduction Safety of Diagnostic Work-up Solid Tumors Arising During... Hematopoietic Tumors Arising... Other Malignant Tumors Arising... Safety of Chemotherapy Metastases of Maternal Tumors... Recommended Therapeutic Abortion... References

 
Cancer complicating pregnancy is a rare coexistence. The incidence is approximately 1 in 1,000 pregnancies. The most common cancers are those more frequently seen during the reproductive age of a woman. Breast cancer, cervical cancer, Hodgkin’s disease, malignant melanoma, and leukemias are the most frequently diagnosed malignancies during gestation.

The diagnostic and therapeutic management of the pregnant patient with cancer is especially difficult because it involves two persons, the mother and the fetus.

In this paper we review: A) the therapeutic and diagnostic management of these patients; B) the safety of diagnostic and therapeutic procedures; C) the metastatic pattern of the maternal tumors to the placenta and fetus, and D) the potential recommendations for therapeutic abortion.

Key Words. Pregnancy • Cancer • Diagnosis • Staging • Treatment

	INTRODUCTION

Top Abstract Introduction Safety of Diagnostic Work-up Solid Tumors Arising During... Hematopoietic Tumors Arising... Other Malignant Tumors Arising... Safety of Chemotherapy Metastases of Maternal Tumors... Recommended Therapeutic Abortion... References

 
The occurrence of cancer in pregnant women is not a common phenomenon. The incidence ranges from 0.07% to 0.1% of all malignant tumors, although a variety of other benign neoplasms (i.e., desmoid tumors, pheochromocytoma) are also seen. The most common malignancies associated with pregnancy include cervical cancer, breast cancer, melanoma, lymphomas, and leukemias (Tables 1 and 2) [1–4].

Clear guidelines for the management of these women are very important. Despite the absence of strict guidelines, the following optimal gold standards should always be followed: A) try to benefit the mother’s life; B) try to treat curable malignant disease of pregnant women; C) try to protect the fetus and newborn from harmful effects of cancer treatment, and D) try to retain the mother’s reproductive system intact for future gestations.

	SAFETY OF DIAGNOSTIC WORK-UP

Top Abstract Introduction Safety of Diagnostic Work-up Solid Tumors Arising During... Hematopoietic Tumors Arising... Other Malignant Tumors Arising... Safety of Chemotherapy Metastases of Maternal Tumors... Recommended Therapeutic Abortion... References

 
Staging Radiodiagnostic Procedures
Ionizing radiation includes gamma rays, x-rays, and particulate radiation. Epidemiological studies have established the potential of ionizing radiation to induce leukemia and solid tumors in children and adults [6,7].The radiation effect on fetal life seems to be dose dependent (Table 3). In addition, the adverse effects of radiation are directly related to the stage of gestation—the earlier the stage, the more detrimental the expected effects (Table 4).

In a large study on 32,000 twins, the relative risk for leukemia and solid tumors was 1.6 and 3.2, respectively [9]. Despite numerous studies that correlate childhood leukemia with prenatal radiation, there is still uncertainty whether it plays a causative or an associative role.

In pregnant women with cancer, staging imaging tests should be limited to those associated with the lowest exposure to ionizing radiation. Abdominal plain films, isotope scans, and computerized tomography should be avoided. In contrast, chest x-ray and abdominal ultrasound are indicated as staging procedures.

In certain cases, i.e., brain tumors or pheochromocytomas, magnetic resonance imaging is recommended since it has the benefit of avoiding ionizing radiation to the fetus.

	SOLID TUMORS ARISING DURING GESTATION

Top Abstract Introduction Safety of Diagnostic Work-up Solid Tumors Arising During... Hematopoietic Tumors Arising... Other Malignant Tumors Arising... Safety of Chemotherapy Metastases of Maternal Tumors... Recommended Therapeutic Abortion... References

 
Breast Cancer

Epidemiology
The incidence of breast cancer during pregnancy is approximately 1 in 3,000 pregnancies [10]. It has been estimated that 0.2%-3.8% of all breast tumors are coincident with pregnancy. Pregnancy-associated breast cancer is defined as carcinoma that is diagnosed during pregnancy or within 1 year postpartum. The median age of these women is 33 years, ranging from 23 to 47 [11].

It is estimated that for an obstetrician managing approximately 250 deliveries annually, he/she would require at least 40 years of clinical practice to see two to three cases of pregnancy-associated breast cancer.

Diagnosis
Pregnant women are at a higher risk of presenting with more advanced disease than nonpregnant women since small lumps cannot be easily detected due to the natural tenderness and engorgement of the breasts during pregnancy and lactation. Average delays of 5 to 7 months are reported.

Most patients present with painless masses, 90% of which are detected by self-examination. Diagnosis of breast cancer should be made as early as possible. Breast examination must be a regular clinical practice to detect persisting and enlarging masses, nipple or skin retraction, other skin changes, or axillary lymphadenopathy.

Due to a difference in radiographic density, the sensitivity of mammography in detecting cancerous changes in breasts of pregnant women is about 68%, while that of ultrasonography is around 93% [12]. Diagnosis may be safely made with a fine-needle aspiration or excisional biopsy under local anesthesia. Zemlickis et al. showed that a pregnant woman has a 2.5-fold higher risk of presenting with disseminated breast cancer than a nonpregnant woman, and a lower chance of being diagnosed in stage I [13].

There are no differences in various histologic types of breast cancer between pregnant and nonpregnant women with cancer. Most of the benign tumors diagnosed during pregnancy are similar to those seen in nonpregnant women, e.g., fibroadenoma, lipomas, and papillomas. However, almost 30% of benign breast lesions, such as lactating adenomas, galactoceles, mastitis, and infarcts, are unique to pregnant or lactating women [14].

Treatment
The strategies for therapeutic management of pregnancy-associated breast cancer are mainly dependent on the disease stage.

Early Breast Cancer (Stages I and II)
Modified radical mastectomy is the treatment of choice for stage I and stage II breast cancer. Radiotherapy should be delayed until after delivery in order to avoid harmful effects on the fetus. Adjuvant chemotherapy—if indicated—should not be administered during the first trimester of gestation. In the studies of Zemlickis et al., and Berry et al., 75% and 91% of pregnant women underwent modified radical or segmental mastectomy, respectively [13,15].

In the study of Petrek et al., the 5-year survival of patients with negative axillary nodes was 82% in both pregnant and nonpregnant women, while the 10-year survival was 77% for pregnant and 75% for nonpregnant women. No statistically significant treatment effect was noted [16].

Advanced Breast Cancer (Stages III and IV)
Radiation therapy should be completely avoided for the benefit of the fetus. Chemotherapy is still indicated after the first trimester of pregnancy. Berry et al. treated 24 pregnant patients suffering from primary or recurrent breast cancer with CMF combination chemotherapy. Chemotherapy was safely administered to all patients after the first trimester [15].

Again, in the Petrek et al. study, the 5-year survival of patients with positive axillary nodes was 47% for pregnant and 59% for nonpregnant women, whereas 10-year survival rates were 28% and 41%, respectively. Statistical analysis showed no difference between pregnant and nonpregnant women [16].

Fetal Outcome
Zemlickis et al. reported that radiation alone or in combination with systemic therapies was given to 73 of the 118 pregnant women, while 26 patients were treated with chemotherapy alone. Concerning fetal outcome, 22 pregnancies were terminated by therapeutic abortion, 12 by miscarriage, and there were 85 deliveries, 21 of which were by cesarean section. Of the 85 deliveries, there were 83 live births and two stillbirths [13] (Table 5).

Therapeutic Abortion
In the 1950s and 1960s, therapeutic abortion was advocated due to concerns for hormonal stimulation of tumor growth or to lack of effective systemic therapy. In the 1980s and 1990s, therapeutic abortion failed to improve survival, and it was found that pregnancy had no effect on the course of the disease. In addition, it was observed that 80% of pregnancy-associated breast cancers were estrogen and progesterone receptor negative. Nowadays, oncologists should consider therapeutic abortion during the first and second trimesters only in aggressive primary breast cancer or in patients with advanced disease, in which prompt treatment is strongly recommended.

Pregnancy After Breast Carcinoma
The effect of pregnancy on survival after successful treatment of breast carcinoma is predominantly related to the stage of the disease. Patients with early stages (stage I and II) show no difference in overall and 5-year survival rates. Patients with stage III disease should consider deferring pregnancy for at least 5 years after treatment, whereas women with stage IV disease should not consider conception at all [17,18] (Table 6).

Epidemiology
Carcinoma of the cervix, being a tumor of the reproductive years, is one of the most common cancers diagnosed during gestation. Reports of the incidence vary between 0.02% and 0.9%. The real incidence during the decade 1980-1990 was 1.2 in 10,000 pregnancies [19–21]. Recently, the incidence has seemed to decline due to better public awareness for early detection.

Diagnosis
Although the diagnosis of cervical cancer in pregnancy can sometimes be delayed, there is adequate evidence that pregnant women have a 3.1-fold higher chance of being diagnosed with stage I disease because of frequent pelvic examinations. [22]. The diagnosis can be safely performed by colposcopy and colposcopy-directed biopsy.

Treatment and Outcome
Since most cases are diagnosed in an early stage, a delay in treatment should be recommended in order to reach fetal maturity and viability. With modern neonatal care, newborn mortality has been dramatically decreased.

In order to avoid perinatal complications, it is preferable to manage abnormal cytologic smears in a conservative way. During the first trimester of pregnancy, it is generally safe to delay cone biopsy since it can increase the overall abortion rate by up to 17%. Conization should be left for the second trimester and for cases where the diagnosis of invasive cancer cannot be made otherwise. Conization in the first trimester is associated with an abortion rate of 33%. Following delivery, conization or hysterectomy should be decided by the obstetrician [4,23].

The overall therapeutic management of pregnancy-associated carcinoma of the cervix, according to the disease stage, is as follows:

1. Stage I or carcinoma in situ. Treatment should be delayed until the fetus has matured. If invasion is less than 3 mm without lymph-vascular space involvement, the pregnant woman should be followed to term and delivered vaginally. If invasion is 3-5 mm and lymph-vascular space is involved, these women may also be followed to term. Afterward, a cesarean section should be performed followed by radical hysterectomy and pelvic lymphadenectomy. If invasion is more than 5 mm, the tumor should be treated as invasive cervical carcinoma while taking into consideration the stage of gestation and the preference of the parents.
   
2. Stage IB (bulky), II, III, and IV. For all these stages, radiotherapy is the treatment of choice. In the case of a viable fetus, cesarean section is preoperatively recommended.
   

In general, cervical cancer does not adversely affect pregnancy. Several retrospective studies have demonstrated no difference in tumor grade or in 5-year survival between pregnant and nonpregnant women with cervical cancer. Also, some reports found no difference in maternal survival between women who delivered vaginally and women who underwent cesarean deliveries [19,22].

Malignant Melanoma

Epidemiology
The real incidence of malignant melanoma during pregnancy is unknown. Smith and Randall, in 1969, reported an incidence of 2.8 per 1,000 deliveries [24]. Generally, it is postulated that melanoma accounts for about 8% of all malignant tumors arising during gestation. However, 30%-35% of women with melanoma are of child-bearing age. From the registry of the German Dermatological Society, it was found that 1% of female melanoma patients were pregnant and 40% were diagnosed during the premenopausal stage [25].

Diagnosis
The diagnosis of melanoma is always made by tumor excision and pathological examination. Tumor thickness, primarily, as well as tumor site remain important prognostic factors for pregnant women with melanoma. The effect of pregnancy on tumor location and thickness is still unclear [4].

Treatment and Outcome
Despite a long-term controversy on the prognosis of pregnancy-associated malignant melanoma, there is now strong evidence that the clinical course of pregnant women with melanoma is similar to that of nonpregnant women. Pregnant patients with early primary lesions and adequate surgical excision have a very good prognosis. In these cases, there is no need for therapeutic abortion, whereas in advanced disease, termination of the pregnancy may be useful [4].

Slingluff and Seigler published a series of 100 cases of pregnancy-associated malignant melanoma. Although they found a higher incidence of nodal involvement compared with matched controls, overall mortality was not statistically different [26].

	HEMATOPOIETIC TUMORS ARISING DURING GESTATION

Top Abstract Introduction Safety of Diagnostic Work-up Solid Tumors Arising During... Hematopoietic Tumors Arising... Other Malignant Tumors Arising... Safety of Chemotherapy Metastases of Maternal Tumors... Recommended Therapeutic Abortion... References

 
Lymphomas

Epidemiology
The incidence of Hodgkin’s disease ranges from 1 in 1,000 to 1 in 6,000 pregnancies [27,28]. Among 775 women with stage IA-IIA Hodgkin’s disease treated with radiotherapy, 3.2% were pregnant [29]. Non-Hodgkin’s lymphoma (NHL) occurring in pregnancy is more rare. Up to 1985, 75 cases of pregnancy-associated NHL were reported in the literature [30].

Diagnosis and Staging
To avoid teratogenicity, a limited staging work-up for Hodgkin’s disease and NHL is mandatory during pregnancy. Staging should always include physical examination, blood tests, chest x-ray, bone marrow biopsy, and abdominal ultrasound. Tomographic and isotope scans are contraindicated.

It seems that pregnant women are not likely to be at a higher stage of their disease when diagnosed than their matched controls. From the 48 women with Hodgkin’s disease and pregnancy managed at the Princess Margaret Hospital between 1958 and 1984, 34 (70.8%) had early-stage disease (stage I and II) and the rest (29.2%) had advanced disease, stages III and IV [31].

Treatment and Outcome
Pregnancy in itself does not affect the course of the lymphoma and survival, while therapeutic abortion does not improve the course of the disease. From the Princes Margaret Hospital experience, no significant difference in the 20-year survival rate between 48 women with pregnancy-associated Hodgkin’s disease and 67 matched controls was found. Of the 50 pregnancies studied, there were 38 live births. No statistically significant differences in gestational age, birth weight, delivery method, malformations, or stillbirth rate were observed [31].

There is also enough evidence from the literature to show that no differences in maternal, pregnancy, or fetal outcomes exist between pregnant women with Hodgkin’s disease or NHL and matched controls [4].

There seems to be no evidence for teratogenic effect of local treatment with supradiaphragmatic radiotherapy, especially in early trimesters, or chemotherapy, mainly given during the second or third trimester of pregnancy [29].

Leukemias

Epidemiology
The real incidence of leukemia during gestation is not well known. It is estimated to range from 1 in 75,000 to 100,000 pregnancies [32–34]. Acute leukemias are more frequent. Among them, acute myeloid leukemia is diagnosed twice as often as lymphatic leukemia. Concerning chronic leukemias, chronic myeloid leukemia (CML) accounts for less than 10% of all cases. Chronic lymphocytic leukemia is very rare since it is a malignancy most commonly detected in the elderly.

Treatment and Outcome
From the existing data in the literature, it seems that leukemia can affect both the pregnancy and the fetus. The treatment of acute leukemia should be started immediately after diagnosis. The therapeutic management of pregnant women with acute leukemia is very difficult, and the final decisions should be made by the hematologist/oncologist, the patient, and the family. Abortion should be recommended during the first trimester of pregnancy, however, if the patient expresses the desire to keep the baby, then nonteratogenic cytostatics should be used. Systemic chemotherapy during later trimesters is not associated with teratogenic risk [35–37].

CML is usually treated conservatively. The successful administration of hydroxyurea and interferon or even of leukapheresis has been reported in single cases. If the option for aggressive treatment (i.e., bone marrow transplantation) has been taken, then this should be delayed until after delivery [38,39].

	OTHER MALIGNANT TUMORS ARISING DURING GESTATION

Top Abstract Introduction Safety of Diagnostic Work-up Solid Tumors Arising During... Hematopoietic Tumors Arising... Other Malignant Tumors Arising... Safety of Chemotherapy Metastases of Maternal Tumors... Recommended Therapeutic Abortion... References

 
Ovarian Cancer
The incidence of ovarian malignancies during pregnancy is estimated to be between 1 in 10,000 and 1 in 100,000 deliveries [40,41]. Around 40% of these tumors are germ-cell tumors. Epithelial ovarian tumors are usually of low stage and low grade. The optimal management of pregnant patients with ovarian cancer is not well established, but several reports found good fetal outcomes with a conservative surgical approach [4].

Endometrial Cancer
Endometrial cancer occurs very rarely during pregnancy. Only 16 cases were reported up to 1996 [4].

Colorectal Cancer
Up to 1985, almost 200 pregnant women with colorectal cancer were reported in the literature [42,43]. Woods et al. report an incidence of 1 in 13,000 deliveries [44]. More than 60% of cases were rectal tumors. There is probably a delay in diagnosis, resulting in the presentation of more advanced stages and poorer prognoses than in nonpregnant patients. This delay could be explained by attributing the symptoms of colorectal cancer to the normal changes of pregnancy [4].

Thyroid Cancer
Thyroid cancer seems to be rare during pregnancy. No endocrine association between maternal hormonal changes and thyroid cancer has been found. Therapeutically, lobectomy with cervical node dissection can be performed. Radioactive iodine should be avoided, and chemotherapy is not effective [45,46].

Central Nervous System Tumors
Intracranial and spinal tumors are extremely rare in pregnancy. Thirty percent of tumors are gliomas, and another 30% are meningiomas. The most common spinal tumor is vertebral hemangioma [47].

	SAFETY OF CHEMOTHERAPY

Top Abstract Introduction Safety of Diagnostic Work-up Solid Tumors Arising During... Hematopoietic Tumors Arising... Other Malignant Tumors Arising... Safety of Chemotherapy Metastases of Maternal Tumors... Recommended Therapeutic Abortion... References

 
The administration of chemotherapy during gestation can induce harmful effects to the fetus, the newborn, and the mother. For the fetus and the newborn, these detrimental effects include malformations, teratogenesis, mutations, carcinogenesis, organ toxicity, and retarded development; for the mother, they include spontaneous abortion and sterility.

Despite the fact that all chemotherapy drugs are capable of crossing the placenta, fetal toxicity is clearly dependent on the time of treatment. In most cases, toxic effects were reported when treatment was given during embryogenesis in the first trimester and less often when administered during later trimesters. The rate of chemotherapy-associated fetal malformation is 12.7%-17%, and that of low birth weight is 40%. In contrast, the usual rate of malformations in the general population is around 1%-3% [48–50].

Among the therapeutic drugs, antimetabolites (aminopterin, methotrexate, 5-fluorouracil, arabinosyl cytosine) and alkylating agents (busulfan, cyclophosphamide, chlorambucil) are the most common drugs reported to induce malformation or to exert teratogenic effects (Table 7). Vinca alkaloids and antibiotics seem to have no effect on the fetus; however, cisplatin is implicated in growth restriction and hearing loss, whereas etoposide is implicated in pancytopenia. No data are available on the effect of taxanes or of other drugs on the fetus. The Toronto Leukemia Study Group data demonstrated that about one-third of all infants exposed in utero to chemotherapy experienced pancytopenia at birth [51–52].

It should be pointed out that most of the available data on the teratogenic risks of chemotherapy are based on case reports and small series. Long-term studies are needed to evaluate the effects of chemotherapy on the mother, the fetus, and the neonate.

In 1986, The Registry of Pregnancies Exposed to Cancer Chemotherapy was established at the National Cancer Institute by J.J. Mulvihill. The purpose of this computerized registry is to clarify the effects of cancer chemotherapy on the developing fetus. It is a collection of published and unpublished outcomes of pregnancies exposed to drugs and radiation. To date, the registry includes 277 pregnancies, 234 abstracted from the medical literature, 40 personally reported cases, and three from other sources. The 277 registered cases include 247 with cancer (52% leukemia, 27% lymphoma, and 18% other cancers) and 30 transplants, autoimmune disorders, or attempted abortions. At present, the registry can provide rapid access, via a Microsoft^® Access database, to specifically relevant cases from the literature as an aid to counseling. The Registry is now located at the University of Oklahoma Medical Center Section of Genetics (940 NE 13th Street, Room B2418, Oklahoma City, OK 73104, USA; telephone: 405-271-3663 or 866-654-3637; fax 405-271-8697; e-mail: John-mulvihill{at}ouhsc.edu) [53–54].

	METASTASES OF MATERNAL TUMORS TO THE PLACENTA AND FETUS

Top Abstract Introduction Safety of Diagnostic Work-up Solid Tumors Arising During... Hematopoietic Tumors Arising... Other Malignant Tumors Arising... Safety of Chemotherapy Metastases of Maternal Tumors... Recommended Therapeutic Abortion... References

 
Vertical transmission of cancer is exceptionally rare, although maternal cells do reach the fetus. From 1866 to 1999, 58 cases of documented maternal malignancy metastatic to the placenta and fetus were reported in the western literature [4,55–58]. The tumors most commonly seen coexisting with pregnancy are not those most commonly found involving the products of conception (placenta and fetus). The most likely way for dissemination is through the hematogenous route. The rarity of this dissemination is probably due to the placental barrier and the fetal immune system.

The most common tumor metastasizing to the placenta or fetus is malignant melanoma, accounting for 30% of all pregnancy-associated tumors. The second most frequent malignancies are leukemia and lymphoma followed by carcinoma of the breast and lung [56]. For more details see Table 8.

	RECOMMENDED THERAPEUTIC ABORTION IN PREGNANT WOMEN WITH CANCER

Top Abstract Introduction Safety of Diagnostic Work-up Solid Tumors Arising During... Hematopoietic Tumors Arising... Other Malignant Tumors Arising... Safety of Chemotherapy Metastases of Maternal Tumors... Recommended Therapeutic Abortion... References

Despite the absence of guidelines, therapeutic abortion during the first trimester of pregnancy could be recommended primarily for locally advanced-stage cervical carcinoma, advanced breast cancer or breast cancer necessitating adjuvant systemic treatment, stage III-IV aggressive NHL or Hodgkin’s disease, and acute leukemia. In addition, any other chemosensitive or nonchemosensitive solid tumor could be included under the same recommendations, provided that the decision follows a thorough discussion among the pregnant patient, the doctor, and the family.

	REFERENCES

Top Abstract Introduction Safety of Diagnostic Work-up Solid Tumors Arising During... Hematopoietic Tumors Arising... Other Malignant Tumors Arising... Safety of Chemotherapy Metastases of Maternal Tumors... Recommended Therapeutic Abortion... References

 

1. Nieminen V, Remes N. Malignancy during pregnancy. Acta Obstet Gynecol Scand 1970;49:315–319.[Medline]
2. Donegan WL. Cancer and pregnancy. CA Cancer J Clin 1983;33:194–214.[Abstract/Free Full Text]
3. Koren G, Lishner M, Farine D, eds. Cancer in Pregnancy. Maternal and Fetal Risks. Cambridge: Cambridge University Press, 1996.
4. Antonelli NM, Dotters DJ, Katz VL et al. Cancer in pregnancy: a review of the literature. Part I-II. Obstet Gynecol Surv 1996;51:125–142.[CrossRef][Medline]
5. Wingo PA, Tong T, Bolden S. Cancer statistics, 1995. CA Cancer J Clin 1995;45:8–30.[Abstract/Free Full Text]
6. Advisory Committee on the Biological Effects of Ionizing Radiation. National Research Council. National Academy of Sciences. The Effects on Populations of Exposure to Low Levels of Ionizing Radiation. Washington, DC: National Academy Press, 1980.
7. Palhemus D, Koch R. Leukemia and medical irradiation. Pediatrics 1959;23:453–461.[Abstract/Free Full Text]
8. Bentur Y. Prenatal irradiation and cancer. In: Koren G, Lishner M, Farine D, eds. Cancer in Pregnancy. Maternal and Fetal Risks. Cambridge: Cambridge University Press, 1996:159-167.
9. Mole RH. Childhood cancer after prenatal exposure to diagnostic x-ray examinations in Britain. Br J Cancer 1990;62:152–168.[Medline]
10. Parente JT, Amsel M, Lerner R et al. Breast cancer associated with pregnancy. Obstet Gynecol 1988;71:861–864.[Medline]
11. Zemlickis D, Lishner M, Degendorfer P et al. Maternal and fetal outcome after breast cancer in pregnancy. Am J Obstet Gynecol 1992;166:781–787.[Medline]
12. Ishida T, Yokoe T, Kasumi F et al. Clinicopathologic characteristics and prognosis of breast cancer patients associated with pregnancy and lactation: analysis of case-control study in Japan. Jpn J Cancer Res 1992;83:1143–1149.[CrossRef][Medline]
13. Zemlickis D, Lishner M, Degendorfer P et al. Maternal and fetal outcome following breast cancer in pregnancy. In: Koren G, Lishner M, Farine D, eds. Cancer in Pregnancy. Maternal and Fetal Risks. Cambridge: Cambridge University Press, 1996:95-106.
14. Byrd BF, Bayer DS, Robertson JC et al. Treatment of breast tumors associated with pregnancy and lactation. Ann Surg 1962;155:940–947.
15. Berry DL, Theriault RL, Holmes FA et al. Management of breast cancer during pregnancy using a standardized protocol. J Clin Oncol 1999;17:855–861.[Abstract/Free Full Text]
16. Petrek JA, Dukoff R, Rogatko A. Prognosis of pregnancy-associated breast cancer. Cancer 1991;67:869–872.[CrossRef][Medline]
17. Averette HE, Mirhashemi R, Moffat FL. Pregnancy after breast carcinoma: the ultimate medical challenge. Cancer 1999;85:2301–2304.[CrossRef][Medline]
18. Gemignani ML, Petrek JA. Pregnancy after breast cancer. Cancer Control 1999;6:272–276.[Medline]
19. Hacker NF, Berek JS, Lagasse LD et al. Carcinoma of the cervix associated with pregnancy. Obstet Gynecol 1982;59:735–746.[Abstract/Free Full Text]
20. Shingleton HM, Orr J. In: Cancer of the Cervix. Philadelphia: JB Lippincott, 1995:344.
21. Duggan B, Muderspach LI, Roman LD et al. Cervical cancer in pregnancy: reporting on planned delay in therapy. Obstet Gynecol 1993;82:598–602.[Medline]
22. Zemlickis D, Lishner M, Degendorfer P et al. Maternal and fetal outcome after invasive cervical cancer in pregnancy. J Clin Oncol 1991;9:1956–1961.[Abstract/Free Full Text]
23. Averette HE, Nasser N, Yankow SL et al. Cervical conization in pregnancy: analysis of 180 operations. Am J Obstet Gynecol 1970;106:543–549.[Medline]
24. Smith RS, Randall P. Melanoma during pregnancy. Obstet Gynecol 1969;34:825–829.[Abstract/Free Full Text]
25. Garbe C. [Pregnancy, hormone preparations and malignant melanoma]. Hautarzt 1993;44:347–352. German.[Medline]
26. Slingluff Jr CL, Seigler HF. Malignant melanoma and pregnancy. Ann Plast Surg 1992;28:95–99.[CrossRef][Medline]
27. Riva HL, Anderson PS, O’Grady JW. Pregnancy and Hodgkin’s disease: a report of eight cases. Am J Obstet Gynecol 1953;66:866–870.[Medline]
28. Stewart HL, Monto RW. Hodgkin’s disease and pregnancy. Am J Obstet Gynecol 1952;63:570–578.[Medline]
29. Woo SY, Fuller LM, Cundiff JH et al. Radiotherapy during pregnancy for clinical stages IA-IIA Hodgkin’s disease. Int J Radiat Oncol Biol Phys 1992;23:407–412.[Medline]
30. Ward FT, Weiss RB. Lymphoma and pregnancy. Semin Oncol 1989;16:397–409.[Medline]
31. Lishner M, Zemlickis D, Degendorfer P et al. Maternal and fetal outcome following Hodgkin’s disease in pregnancy. In: Koren G, Lishner M, Farine D, eds. Cancer in Pregnancy. Maternal and Fetal Risks. Cambridge: Cambridge University Press, 1996:107-115.
32. Yahia C, Hyman GA, Phillips LL. Acute leukemia and pregnancy. Obstet Gynecol Surv 1958;13:1–21.[Medline]
33. Catanzarite VA, Ferguson 2nd JE. Acute leukemia and pregnancy: a review of management and outcome, 1972-1982. Obstet Gynecol Surv 1984;39:663–678.[Medline]
34. Haas JF. Pregnancy in association with a newly diagnosed cancer: a population-based epidemiologic assessment. Int J Cancer 1984;34:229–235.[Medline]
35. Reynoso EE, Shepherd FA, Messner HA et al. Acute leukemia during pregnancy: the Toronto Leukemia Study Group experience with long-term follow-up of children exposed in utero to chemotherapeutic agents. J Clin Oncol 1987;5:1098–1106.[Abstract/Free Full Text]
36. McLain Jr CR. Leukemia in pregnancy. Clin Obstet Gynecol 1974;17:185–194.[CrossRef][Medline]
37. Caligiuri MA, Mayer RJ. Pregnancy and leukemia. Semin Oncol 1989;16:388–396.[Medline]
38. Delmer A, Rio B, Bauduer F et al. Pregnancy during myelosuppressive treatment for chronic myelogenous leukemia. Br J Haematol 1992;82:783–784.[Medline]
39. Jackson N, Shukri A, Ali K. Hydroxyurea treatment for chronic myeloid leukaemia during pregnancy. Br J Haematol 1993;85:203–204.[Medline]
40. Jolles CJ. Gynecologic cancer associated with pregnancy. Semin Oncol 1989;16:417–424.[Medline]
41. Atar E, Dgani R, Shoham Z et al. [Malignant ovarian tumors in pregnancy]. Harefuah 1990;119:146–148. Hebrew.[Medline]
42. Bernstein MA, Madoff RD, Caushaj PF. Colon and rectal cancer in pregnancy. Dis Colon Rectum 1993;36:172–178.[CrossRef][Medline]
43. Nesbitt JC, Moise KJ, Sawyers JL. Colorectal carcinoma in pregnancy. Arch Surg 1985;120:636–639.[Abstract]
44. Woods JB, Martin Jr JN, Ingram FH et al. Pregnancy complicated by carcinoma of the colon above the rectum. Am J Perinatol 1992;9:102–110.[Medline]
45. Kobayashi K, Tanaka Y, Ishiguro S et al. Rapidly growing thyroid carcinoma during pregnancy. J Surg Oncol 1994;55:61–64.[Medline]
46. Ringenberg QS, Doll DC. Endocrine tumors and miscellaneous cancers in pregnancy. Semin Oncol 1989;16:445–455.[Medline]
47. Roelvink NCA, Kamphorst W, van Alphen HAM et al. Pregnancy-related primary brain and spinal tumors. Arch Neurol 1987;44:209–215.[Abstract]
48. Doll DC, Ringenberg QS, Yarbro JW. Antineoplastic agents and pregnancy. Semin Oncol 1989;16:337–346.[Medline]
49. Schapira DV, Chudley AE. Successful pregnancy following continuous treatment with combination chemotherapy before conception and throughout pregnancy. Cancer 1984;54:800–803.[CrossRef][Medline]
50. Sweet Jr DL, Kinzie J. Consequences of radiotherapy and antineoplastic therapy for the fetus. J Reprod Med 1976;17:241–246.[Medline]
51. Zemlickis D, Lishner M, Koren G. Review of fetal effects of cancer chemotherapeutic agents. In: Koren G, Lishner M, Farine D, eds. Cancer in Pregnancy. Maternal and Fetal Risks. Cambridge: Cambridge University Press, 1996:168-180.
52. Zemlickis D, Lishner M, Degendorfer P et al. Fetal outcome following in utero exposure to cancer chemotherapy: the Toronto study. In: Koren G, Lishner M, Farine D, eds. Cancer in Pregnancy. Maternal and Fetal Risks. Cambridge: Cambridge University Press, 1996:181-188.
53. Mulvihill JJ, Stewart KR. A registry of pregnancies exposed to chemotherapeutic agents. Teratology 1986;33:80.
54. Randall T. National registry seeks scarce data on pregnancy outcomes during chemotherapy. JAMA 1993;269:323.
55. Friedreich N. Beitrage zur Pathologie des Krebses. Virchows Arch (Pathol Anat) 1866;36:
56. Dildy 3rd GA, Moise Jr KJ, Carpenter Jr RJ et al. Maternal malignancy metastatic to the products of conception: a review. Obstet Gynecol Surv 1989;44:535–540.[Medline]
57. Potter JF, Schoeneman M. Metastasis of maternal cancer to the placenta and fetus. Cancer 1970;25:380–388.[CrossRef][Medline]
58. Catlin EA, Roberts JD, Erana R et al. Transplacental transmission of natural-killer-cell lymphoma. N Engl J Med 1999;341:85–91.[Free Full Text]

This article has been cited by other articles:

				C.H. t. Hove, J.M. Zijlstra-Baalbergen, E.F.I. Comans, and R.M. van Elburg An unusual hotspot in a young woman with Hodgkin's lymphoma Haematologica, January 1, 2008; 93(1): e14 - e15. [Abstract] [Full Text] [PDF]

				D. Pereg, G. Koren, and M. Lishner The treatment of Hodgkin's and non-Hodgkin's lymphoma in pregnancy Haematologica, September 1, 2007; 92(9): 1230 - 1237. [Abstract] [Full Text] [PDF]

				M. S. Lam Treatment of Burkitt's Lymphoma During Pregnancy Ann. Pharmacother., November 1, 2006; 40(11): 2048 - 2052. [Abstract] [Full Text] [PDF]

				M. Beyeler, J. Hafner, E. Beinder, J.-C. Fauchere, S. J. Stoeckli, M. Fehr, and R. Dummer Special Considerations for Stage IV Melanoma During Pregnancy Arch Dermatol, September 1, 2005; 141(9): 1077 - 1079. [Full Text] [PDF]

This Article Abstract Full Text (PDF) An erratum has been published eLetters: Submit a response to this article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pavlidis, N. A. Search for Related Content PubMed PubMed Citation Articles by Pavlidis, N. A.