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Keywords:

  • breast carcinoma;
  • pregnancy;
  • recommendation;
  • chemotherapy

Abstract

  1. Top of page
  2. Abstract
  3. Epidemiology of Breast Carcinoma in Pregnancy
  4. Pathology
  5. Prognosis
  6. Methodology
  7. Diagnosis
  8. Treatment of Breast Carcinoma during Pregnancy
  9. Multidisciplinary Approach
  10. Monitoring of the Pregnancy
  11. Long-Term Implications for the Child
  12. Conclusions
  13. Acknowledgements
  14. REFERENCES

BACKGROUND

Breast carcinoma during pregnancy (BCP) is a difficult clinical situation, as it appears to put the health of the mother in conflict with that of the fetus.

METHODS

An international expert meeting was conducted to form guidelines on how to diagnose and treat women with BCP.

RESULTS

The goal for treatment of the pregnant woman with breast carcinoma is the same as that of the nonpregnant breast carcinoma patient: local control of disease and prevention of systemic metastases. However, certain treatment modalities need to be modified because of the potential for adverse effects on the fetus. There is evidence to support the safety of anthracycline-based chemotherapy during the second and third trimesters of pregnancy (Oxford Level of Evidence [LOE] 2b). Because of the lack of evidence, the expert opinion was not to recommend the routine use of newer cytotoxic drugs like the taxanes during pregnancy (LOE 5).

CONCLUSION

The recommendations provided should help to reach informed decision making by the patient. The ongoing prospective collection of data on BCP, such as that at the University of Texas M.D. Anderson Cancer Center (UTMDACC) and that of the German Breast Group/Breast International Group (GBG/BIG), is necessary to further our knowledge regarding the treatment of this unique group of breast carcinoma patients. Cancer 2006. © 2005 American Cancer Society.

Breast carcinoma is one of the most commonly diagnosed cancers during pregnancy. There is almost always a perceived conflict between the optimal therapy of the mother with breast carcinoma and the well-being of the fetus. The pregnant breast carcinoma patient, her family, and her medical team may be in conflict, because treatment of the cancer may compromise the fetus. However, insufficient treatment of the breast carcinoma, presumed to protect the fetus, may compromise the health of the mother.

An interdisciplinary team of obstetrician gynecologists, medical oncologists, radiation oncologists, surgeons, pediatricians, geneticists, psychologists, and other members of the medical team is required to formulate and implement the treatment plan.

Epidemiology of Breast Carcinoma in Pregnancy

  1. Top of page
  2. Abstract
  3. Epidemiology of Breast Carcinoma in Pregnancy
  4. Pathology
  5. Prognosis
  6. Methodology
  7. Diagnosis
  8. Treatment of Breast Carcinoma during Pregnancy
  9. Multidisciplinary Approach
  10. Monitoring of the Pregnancy
  11. Long-Term Implications for the Child
  12. Conclusions
  13. Acknowledgements
  14. REFERENCES

From historical case series, the incidence of breast carcinoma in pregnancy is estimated to be about 1 in 3000.1, 2 It is believed that the incidence of breast carcinoma during pregnancy (BCP) will increase as more women delay child-bearing because the incidence of breast carcinoma increases with increasing age. In a 1984 population-based study from the former German Democratic Republic (GDR), for the years 1970–1979,3 the incidence of cancer in pregnancy was 0.02 for women age 15–32, rising to 2.3 in women over 40 years of age. However, in the GDR of the 1970s women tended to have their children in their early 20s, whereas in modern-day Germany the trend is for women to have their first child when over the age of 30.4 A similar trend in age at first childbirth has been observed in the U.S.5

Pathology

  1. Top of page
  2. Abstract
  3. Epidemiology of Breast Carcinoma in Pregnancy
  4. Pathology
  5. Prognosis
  6. Methodology
  7. Diagnosis
  8. Treatment of Breast Carcinoma during Pregnancy
  9. Multidisciplinary Approach
  10. Monitoring of the Pregnancy
  11. Long-Term Implications for the Child
  12. Conclusions
  13. Acknowledgements
  14. REFERENCES

The predominant histology is invasive ductal.6–8 Invasive lobular carcinoma has been diagnosed infrequently in pregnant women and in young nonpregnant women.9 The majority of breast tumors in pregnant women are high grade and lymphovascular invasion is common.10–12 Moreover, most tumors are hormone-independent, as demonstrated in all series investigated (Table 1) In the only prospective series, by Middleton et al.,12 of women with BCP, 28% of the tumors were estrogen receptor (ER)-positive and 24% were progesterone receptor (PR)-positive by immunohistochemistry compared with 45% and 36%, respectively, of nonpregnant young women with breast carcinoma studied by Maru et al.13 Hormone-positive disease is age-related and is seen more often in postmenopausal women.

Table 1. Published Studies Examining Selected Pathologic Features of Breast Cancer Diagnosed during Pregnancy or the Year after Delivery (PABC)
AuthorStudy designNo. subjectsHistologyNuclear gradeER and PRHer-2/neu
  • PABC: pregnancy-associated breast cancer; ER: estrogen receptor; PR: progesterone receptor.

  • a

    Bonnier P, Romain S, Dilhuydy JM, et al. Influence of pregnancy on the outcome of breast cancer: a case control study. Int J Cancer. 1997;72:720-727.

  • b

    Reed W, Sandstad B, Holm R, Nesland JM. The prognostic impact of hormone receptors and c-erbB-2 in pregnancy-associated breast cancer and their correlation with BRCA1 and cell cycle motor. Int J Surg Pathol. 2003;11:65-74.

Ishida et al.11Case–control72 cases (pregnant); 120 cases (lactating); 191 controlsNo differenceNot examinedFewer ER (+) pregnant patients; fewer ER(+) and PR(+) pregnant and lactating womenNot examined
Elledge et al.14Case–control15 cases (pregnant); 411 controlsNot examinedNot examinedNo difference in ER(+) and PR(+)58% of cases Her-2/neu (+) vs. 16% of controls
Tobon and Horowitz7Retrospective case series14 cases93% had invasive ductal carcinomaNot examinedER (–) or low in 50%; PR (–) in 64%Not examined
Bonnier et al.aCase–control154 cases PABC; 308 controlsNo differenceNo difference in histoprognostic gradePregnant women less likely to be ER(+) or PR(+)Not examined
Shousha10Case–control14 cases PABC; 13 controlsInvasive ductal histology: 71% PABC vs. 69% controlsPoorly differentiated: 80% PABC vs. 33% controlsER(–): 50% PABC vs. 9% controls PR(–): 70% PABC vs. 36% controlsHer-2/neu (+): 44% PABC vs. 18% controls
Middleton et al.12Prospective case series38 cases (pregnant) and 1 PABC100% invasive ductal carcinomaPoorly differentiated: 84%ER (–): 72% PR (–): 76%Her-2/neu (+): 28%
Reed et al.bRetrospective case series122 PABC (20 pregnant)invasive ductal carcinoma 82%95% G2-3ER (–): 66% PR (–): 72%Her-2/neu (+): 44%

While Elledge et al.14 found 7 out of 12 pregnant patients (58%) to be positive for Her2/neu, Middleton et al.12 did not find any difference in the Her2/neu expression rate (28%) in the M.D. Anderson series of pregnant women (n = 38) with breast carcinoma compared with that reported in young nonpregnant women with breast carcinoma12, 15 (Table 1).

It appears that the histopathologic and immunohistochemical findings of the tumors of pregnant women with breast carcinoma are similar to those of nonpregnant young women with breast carcinoma. Thus, it is more likely that age at diagnosis rather than the pregnancy determines the biologic features of the tumor.

Table 1 summarizes the majority of studies that have examined the pathologic characteristics of pregnancy-associated breast carcinoma and cancer diagnosed during pregnancy.

Prognosis

  1. Top of page
  2. Abstract
  3. Epidemiology of Breast Carcinoma in Pregnancy
  4. Pathology
  5. Prognosis
  6. Methodology
  7. Diagnosis
  8. Treatment of Breast Carcinoma during Pregnancy
  9. Multidisciplinary Approach
  10. Monitoring of the Pregnancy
  11. Long-Term Implications for the Child
  12. Conclusions
  13. Acknowledgements
  14. REFERENCES

Based on a limited number of retrospective case–control studies, the prognosis of women with BCP does not appear to differ from that of nonpregnant patients of the same age and stage of disease.16–18 Conventionally, it was believed that the prognosis was worse; however, the worse prognosis was probably due to advanced stage at diagnosis or less standardized therapy (Table 2).

Table 2. Selected Studies Comparing Prognosis of Patients with Pregnancy-Associated Breast Cancer and Nonpregnant Controls
AuthorNumber of patientsSurvival typeSubgroupSurvival rate PABC %Survival rate non-PABC %P-value
  • PABC: pregnancy-associated breast cancer; OAS: overall survival; RFS: recurrent-free survival; MFS: metastatic free survival; N0: nodal negative; N+: nodal positive.

  • a

    Nugent P, O'Connell TX. Breast cancer and pregnancy. Arch Surg. 1985;120:1221-1224.

  • b

    Chang YT, Loong CC, Wang HC, Jwo SC, Lui WY. Breast cancer and pregnancy. Zhongha Yi Xue Za Zhi. 1994;54:223-229.

  • c

    Guinee VF, Olsson H, Moller T, et al. Effect of pregnancy on prognosis for young women with breast cancer. Lancet. 1994;343:1587-1589.

  • d

    Anderson BO, Petrek JA, Byrd DR, Senie RT, Borgen PI. Pregnancy influences breast cancer stage at diagnosis in women 30 years of age and younger. Am J Obstet Gynecol. 1996;3:204-211.

  • e

    Bonnier P, Romain S, Dilhuydy JM, et al. Influence of pregnancy on the outcome of breast cancer: a case control study. Int J Cancer. 1997;72:720-727.

Nugent and O'Connella19 PABC 157 controls5-yr OASAll5656n.s.
Petrek et al.1763 PABC5-yr OASAll6173n.s.
   N08282n.s.
   N+4759n.s.
  10-yr OASall4562n.s.
   N07775n.s.
   N+2541n.s.
Ishida et al.11192 PABC/191controls10-yr OASAll55790.001
   N085930.05
   N+37620.01
Zemlickis et al.47118/102 PABC 269 controls10-yr OASAll40480.6
Chang et al.b21 PABC 199 controls5-yr OASAll5770n.s.
Guinee et al.c26 pregnant (66 PABC)5-yr OASAll4070< 0.0001
Anderson et al.d22 PABC 205 controls10-yr OASI-IIA7374n.s.
   IIB-IIIA1747 
Bonnier et al.e154 PABC (62 pregnant) 308 controls5-yr RFSall69810.01
  5-yr MFSall45680.0009
   N06377n.s.
   N+31630.0001
  5-yr OASall61750.001

Methodology

  1. Top of page
  2. Abstract
  3. Epidemiology of Breast Carcinoma in Pregnancy
  4. Pathology
  5. Prognosis
  6. Methodology
  7. Diagnosis
  8. Treatment of Breast Carcinoma during Pregnancy
  9. Multidisciplinary Approach
  10. Monitoring of the Pregnancy
  11. Long-Term Implications for the Child
  12. Conclusions
  13. Acknowledgements
  14. REFERENCES

Definition of population to be discussed

Pregnancy-associated breast carcinoma (PABC) is defined as breast carcinoma that occurs during pregnancy, or the lactation period up to 1 year after the end of pregnancy. We focused on BCP because breast carcinoma during the lactation period or thereafter can be assessed and treated according to standard guidelines.19, 20

How were these guidelines generated and evaluated?

In September 2003, physician researchers from a number of countries who had an interest in BCP (Italy, United States, England, and Germany) were invited to participate in a symposium on this topic. Those invited to participate had published an article or a review of BCP or were specialists in the interdisciplinary treatment of BCP (pharmacologists, geneticists, obstetricians). Participants were asked to present their own data on the treatment of breast carcinoma during pregnancy or to present summaries of literature published thus far. On the basis of the data presented by the participants, as well as the experience of the individuals participating in the symposium, the guidelines were prepared. Richard Theriault, a medical oncologist at the University of Texas M.D. Anderson Cancer Center, also reviewed the guidelines developed.

Since it is not feasible to conduct ethical prospective randomized clinical trials in pregnant breast carcinoma patients, the data reviewed for the establishment of these guidelines was generated primarily from case reports, case-control studies, and historical cohort studies, although there is one prospective cohort of pregnant patients from which data were collected. The level of evidence is therefore not higher than 3 (2b chemotherapy), the Oxford Levels of Evidence (LOE) was used, where appropriate.21 Words used in PubMed were “breast carcinoma” and “pregnancy.” Thus, given the quality and quantity of the data available on this topic, some of the recommendations express the educated opinions of the authors.

Diagnosis

  1. Top of page
  2. Abstract
  3. Epidemiology of Breast Carcinoma in Pregnancy
  4. Pathology
  5. Prognosis
  6. Methodology
  7. Diagnosis
  8. Treatment of Breast Carcinoma during Pregnancy
  9. Multidisciplinary Approach
  10. Monitoring of the Pregnancy
  11. Long-Term Implications for the Child
  12. Conclusions
  13. Acknowledgements
  14. REFERENCES

Physical examination

All women who are pregnant should have a clinical breast examination as part of the first pregnancy physical examination. For women 35 years of age or older and considering becoming pregnant by natural or assisted means, obstetrician/gynecologists should follow their country's guidelines regarding the age at which to perform baseline and routine screening mammography.

Imaging of the breast and nodal basins during pregnancy

Although the majority of breast masses found during pregnancy will not be malignant, a clinically suspicious or persistent breast and/or axillary mass should be imaged and biopsied, especially if imaging fails to confirm a benign etiology for the mass. There are only limited data on the use of breast diagnostic imaging procedures during pregnancy.22, 23

With adequate abdominal shielding, mammography presents little risk to the fetus. A dose of 200–400 mGy is delivered by standard bilateral mammography using modern technology. That would result in less than 50 mrad (0.5 μGy) exposure to the embryo/fetus, well below the level of 10 rad (100 mGy) that increases the risk of fetal malformations by 1%.24 This is less than the estimated environmental exposure of 2 mGy per week. Mammography is the most intensive studied imaging procedure during pregnancy and the only one to rule out extensive microcalcifications and should therefore be used if it is necessary.

Although the reports on the utility of breast and nodal basin ultrasound are limited, this modality may be of benefit in the evaluation of a breast mass and should pose no harm to the developing fetus.22 Some of the sonographic signs (posterior acoustic enhancement, marked cystic component) were somewhat different from the appearance of breast carcinoma in nonpregnant women.25

Because of a lack of data demonstrating its efficacy, the concern over the safety of gadolinium and the difficulty of positioning the pregnant patient on her stomach, we do not recommend magnetic resonance imaging (MRI) in the diagnosis of BCP.

Pathologic diagnosis of breast carcinoma during pregnancy

Although fine-needle aspiration (FNA) can be used to diagnose a breast mass in a pregnant patient, a core or excisional biopsy is required for a definitive diagnosis of invasive cancer.26, 27 The potential for the development of a subsequent milk fistula after core or excisional biopsy is overestimated, with very few reports in the literature.28, 29 To avoid misinterpretation and a false-negative result in doubtful cases, a second opinion slide review at a cancer center is recommended. The risk of false-positive results is negligible in the hands of experienced cytologists.

Staging evaluation of breast carcinoma during pregnancy

Depending on the clinical stage at presentation, a complete staging evaluation should be performed including a chest X-ray with abdominal shielding, an ultrasound of the liver (MRI if necessary), and a screening noncontrast MRI of the thoracic and lumbar spine to exclude bone metastases. Computed tomography (CT) scans and bone scans are not recommended during pregnancy because of concerns with regard to the amount of radiation exposure to the developing fetus with these techniques.

Treatment of Breast Carcinoma during Pregnancy

  1. Top of page
  2. Abstract
  3. Epidemiology of Breast Carcinoma in Pregnancy
  4. Pathology
  5. Prognosis
  6. Methodology
  7. Diagnosis
  8. Treatment of Breast Carcinoma during Pregnancy
  9. Multidisciplinary Approach
  10. Monitoring of the Pregnancy
  11. Long-Term Implications for the Child
  12. Conclusions
  13. Acknowledgements
  14. REFERENCES

The treatment of BCP should conform as closely as possible to standardized protocols for patients without concomitant pregnancy.19, 20

Figures 1A and 1B are flow charts of proposed treatment recommendations for treating a patient with BCP. These flow charts are meant to guide treatment discussions. Every BCP patient requires an individual therapeutic decision that is formulated taking into consideration the gestational age at first presentation, the patient's stage of disease, and the preferences of the patient and her family.

thumbnail image

Figure 1. Algorithms for treating breast carcinoma during pregnancy at (A) less than 12–14 weeks of gestation at time of histologic diagnosis and at (B) 12–34 weeks of gestation at time of histologically confirmed diagnosis. At greater than the 34th week of gestation at time of histologic diagnosis, the algorithm is to immediately deliver if the patient has inflammatory or highly aggressive disease; otherwise, plan delivery when fetal maturation is appropriate, and begin therapy thereafter. PST: primary systemic chemotherapy; AST: adjuvant systemic therapy (includes chemotherapy and/or hormonal therapy); LABC: locally advanced breast carcinoma (T3 and T4).

Download figure to PowerPoint

Local treatment of breast carcinoma during pregnancy

Surgery.

Breast surgery can be safely performed during all trimesters of pregnancy with minimal risk to the developing fetus.30, 31 The surgeon and the patient may choose to wait until the 12th week of gestation has been completed because the risk of a spontaneous abortion is highest before the 12th week of gestation.32 During surgery, monitoring of the fetus should take place depending on gestational age.

From published reports, the majority of pregnant patients with breast carcinoma have had mastectomies, most likely because of concerns over radiation during pregnancy, the stage at presentation, and patterns of practice.11, 33 Breast-conserving surgery with axillary lymph node dissection may be possible, especially for women who are diagnosed in the third trimester or for women whose more advanced stage at presentation warrants the use of neoadjuvant chemotherapy before surgery such that surgery would be performed later in the pregnancy or even postpartum.34, 35

Sentinel lymph node biopsy has not been systematically evaluated in the BCP patient. The estimated dose of radiation to the fetus through the use of technetium has been estimated to be low, and some have expressed the opinion that pregnant patients could be offered sentinel lymph node biopsy after counseling regarding the amounts of radiation involved, calculated to be a maximum of 4.3 mGy.36, 37 Isosulfan blue dye mapping is not recommended in pregnant patients in the U.S. because it has not been approved by the Federal Drug Administration (FDA) for pregnant women and anaphylaxis has been observed with the use of this dye.38, 39 Given that the sensitivity of sentinel lymph node mapping is reduced when only one modality is used, the clinically node-negative BCP patient and her breast surgeon should discuss the potential efficacy and safety of a sentinel lymph node biopsy before proceeding with it (LOE 5).

Radiation.

External beam radiation necessary for the completion of breast conservation or postmastectomy radiation is contraindicated during pregnancy because of the risks associated with fetal exposure to radiation. The most crucial interval for radiation exposure is the first trimester of gestation (before the completion of organogenesis). Radiation doses of 10–90 cGy (0.1–0.9 Gy) in the first trimester have been associated with an increased risk of mental retardation, whereas an exposure greater than 1 Gy is always detrimental.40 If a standard dose of 50–60 Gy is used for radiation of the remaining breast or the chest wall, the fetus will receive a minimum of 2 cGy (2.1–7.6 cGy) in the first trimester, 2.2–24.6 cGy in the second trimester, and 2.2–58.6 cGy in the third trimester.24 Therefore, in the BCP patient radiation should be postponed until after delivery, although the risk to the fetus during radiotherapy for supradiaphragmatic Hodgkin disease appears to be minimal, provided special attention is paid to the treatment techniques and the fetus is adequately shielded.41 However, the need of immediate radiotherapy in breast carcinoma, where it is usually postponed after chemotherapy and surgery have been completed, and Hodgkin disease is different.

Systemic therapy for breast carcinoma during pregnancy

Only limited data on the use of chemotherapy during pregnancy are available. The overall incidence of major congenital malformations after using cytotoxic drugs has been reported to be approximately 3%, but the baseline population risk of major congenital malformations is reported to be 2–3%.42 The risk of teratogenicity of drugs used in breast carcinoma chemotherapy depends on multiple factors, including fetal gestational age and the agent itself. There is no increased risk during the preimplantation period. Data from case series and registries have reported that the risk of congenital malformation from chemotherapeutic exposures in the first trimester range from 10–20%, whereas in the second and third trimester the risk declines to approximately 1.3%.43–45 However, fetal exposure to antineoplastic agents for a variety of malignancies may lead to growth retardation and hematologic cytotoxicity.46

The University of Texas M.D. Anderson Cancer Center has reported the largest prospective series of BCP patients (n = 24) treated with cytotoxic chemotherapy in the second and third trimesters. The authors prospectively evaluated the treatment of BCP patients with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC; F: 500 mg/m2 Days 1+4; A: 50 mg/m2 continuous 72-hr Days 1–3; C: 500 mg/m2 Day 1 of a 3-wk cycle). They reported no significant complications for the fetus or the infant.33 Based on these data, it appears that anthracycline-based chemotherapy (FAC) in the second and third trimesters can be given with minimal risk to the developing fetus (LOE 2b).

Limited data suggest that the infants of BCP patients treated with chemotherapy might have earlier delivery dates; chemotherapy should not be given after the 35th week of gestation, if possible, in order to minimize the risk of neutropenia at the time of delivery.47

There are no prospective studies in which in utero drug concentrations and/or fetal tissue drug levels have been determined in BCP patients and their children. It is recommended to use the same dosages for the anthracycline-based chemotherapy in the treatment of BCP patients as in nonpregnant patients. The pharmacokinetics of cytotoxic drugs in BCP patients requires further study.

Other systemic therapy for breast carcinoma during pregnancy.

There is evidence that methotrexate should not be given in the first trimester of pregnancy if the intent is to maintain pregnancy. It is an abortifacient. When given in the first trimester it has been reported to cause severe fetal malformations known as the “aminopterin syndrome,” with cranial dysostosis as the most consistent anomaly (LOE 4).44, 43 Thus far, the use of newer therapeutic agents such as docetaxel and paclitaxel in BCP patients is limited to case reports (LOE 5).48–50 There are data that show a strong placental expression of drug-extruding transporters like P-glycoprotein (PgP) and others (e.g., BCRP-1) that suggest that tubulin-binding agents like paclitaxel and vincalkaloids can be safely given during the second and third trimesters.51 Absence or pharmacologic blocking of placental PgP profoundly increases fetal drug exposure.52 There is one published case report on the use of trastuzumab in a BCP patient which was associated with reversible anhydramnios (LOE 5).53

Hormonal therapy.

Hormone treatment, if indicated, should started after delivery and after completion of chemotherapy. Neonatal defects from tamoxifen have been described in the genital tract in female mice.54 Although tamoxifen has safely been given in patients with metastatic breast carcinoma without damage to the child,55, 56 there are other reports of birth defects such as Goldenhar syndrome57 and ambiguous genitalia58 in children born to women exposed to tamoxifen. Although Clark59 reported no fetal abnormalities in 85 women who became pregnant while on tamoxifen for breast carcinoma prevention, tamoxifen is not recommended during pregnancy (LOE 4).

Supportive care

Supportive treatment for anthracycline-based chemotherapy can be given according to the general recommendations, including use of a 5HT3-serotonin antagonist and steroids.60 One case–control study found a statistically significant association between first-trimester exposure to corticosteroids and cleft palate in newborns, even when controlled for potential confounding factors.61 Thereafter, their application seems safe. No developmental toxicity has been reported in rats and rabbits exposed to the 5HT3-antagonist ondansetron at doses 70 times higher than those used in humans.62 The use of ondansetron during the first trimester does not appear to cause malformations in humans.63, 64 Considering that BCP patients are treated with anthracycline-based chemotherapy (preferably in the second and third trimesters), corticosteroids and ondansetron should not cause significant risks of fetal malformations. However, in the first trimester corticosteroids should be omitted (LOE 3b).

Granulocyte colony-stimulating factor (G-CSF) and erythropoetin have been used safely in pregnant patients and their use should follow current guidelines for growth factor support during chemotherapy.65, 66

Multidisciplinary Approach

  1. Top of page
  2. Abstract
  3. Epidemiology of Breast Carcinoma in Pregnancy
  4. Pathology
  5. Prognosis
  6. Methodology
  7. Diagnosis
  8. Treatment of Breast Carcinoma during Pregnancy
  9. Multidisciplinary Approach
  10. Monitoring of the Pregnancy
  11. Long-Term Implications for the Child
  12. Conclusions
  13. Acknowledgements
  14. REFERENCES

Genetic counseling

Since breast carcinoma induced by inherited mutations of breast carcinoma genes like BRCA1 or BRCA2 occurs at a significantly earlier age than sporadic breast carcinoma, women with BCP may have an increased risk for these predisposing mutations. In a population-based study from Sweden, significantly more women with BRCA1 mutations had pregnancy-associated breast carcinoma (odds ratio [OR] 3.9; 95% confidence interval [CI], 1.4–10.8) than those with BRCA2 mutations (OR 1.9; 95% CI, 0.5–7.0).67 In a multicenter case–control study in Japan, a family history of breast carcinoma was three times more common in pregnant and lactating women than in other patients with this disease.11 Genetic counseling is recommended for all women who have BCP.

Psychological counseling

Cancer during pregnancy is a stressful situation. Depending on the patient's emotional support and beliefs, it may be appropriate to engage the expertise of other members of the healthcare team such as psychologists, social workers, and a chaplain. A supportive patient–physician relationship is required, as is close collaboration and feedback of all disciplines involved in the patient's care, aiming to assist the patient and her partner toward achieving a true informed consent and commitment to treatment.68, 69 Ongoing psychological support during treatment and delivery should be available for the patient and her family.

Monitoring of the Pregnancy

  1. Top of page
  2. Abstract
  3. Epidemiology of Breast Carcinoma in Pregnancy
  4. Pathology
  5. Prognosis
  6. Methodology
  7. Diagnosis
  8. Treatment of Breast Carcinoma during Pregnancy
  9. Multidisciplinary Approach
  10. Monitoring of the Pregnancy
  11. Long-Term Implications for the Child
  12. Conclusions
  13. Acknowledgements
  14. REFERENCES

Given that there are no evidence-based data that suggest that prenatal care is different in BCP patients, the mother and fetus can be monitored with standard prenatal care. Before starting chemotherapy an ultrasound of the fetus should be performed to ensure that the fetus appears normal and that the gestational age and date of delivery have been estimated. Evaluation for fetal growth should be performed before every cycle of chemotherapy. The maternal/fetal healthcare team may recommend amniocentesis after the initial assessment of the BCP patient if the fetus is thought to be at higher than average risk for karyotype abnormalities or if there are abnormalities detected by ultrasound that warrant further investigation.

In case of abnormalities such as growth retardation, oligohydramnios, or severe anemia of the mother, Doppler ultrasound of the cord vessels should be performed. In the case of abnormal findings, more stringent monitoring of the fetus or even preterm delivery might be necessary.

Pregnancy-related complications such as preeclampsia and preterm labor should be treated based on standard national recommendations.70, 71

Timing of delivery

In the BCP patient, labor can be induced or cesarean section performed when the maturation of the fetus is sufficient. Timing of delivery can be optimized in relation to the treatment of the mother's breast carcinoma. If chemotherapy is planned to continue after delivery, vaginal delivery may be less likely to delay the initiation of that chemotherapy because of the lower morbidity compared with a cesarean section.72 However, the patient's personal preferences and previous obstetric history need to be considered in this decision. Delivery should take place in a hospital with neonatal support should neonatal complications arise.

Although placental metastases in breast carcinoma are rare, the placenta should be histopathologic examined for metastases.73, 74 Metastases to the fetus have never been described in breast carcinoma.

It is recommended that delivery occur approximately 3 weeks after the last dose of anthracycline-based chemotherapy so as to minimize the risk of maternal and fetal neutropenia and subsequent infection. The platelet count should be sufficient to prevent bleeding complications.

The first dose of chemotherapy should be given after adequate time to recover from delivery and to minimize the risk of infection. If treatment is to continue postpartum, breast-feeding during chemotherapy and hormonal therapy is contraindicated, as most of the agents used can be excreted in breast milk.75

Long-Term Implications for the Child

  1. Top of page
  2. Abstract
  3. Epidemiology of Breast Carcinoma in Pregnancy
  4. Pathology
  5. Prognosis
  6. Methodology
  7. Diagnosis
  8. Treatment of Breast Carcinoma during Pregnancy
  9. Multidisciplinary Approach
  10. Monitoring of the Pregnancy
  11. Long-Term Implications for the Child
  12. Conclusions
  13. Acknowledgements
  14. REFERENCES

For the newborn, early and reversible toxicities secondary to cytotoxic treatment of malignancies in a pregnant woman are principally anemia, neutropenia, and alopecia, and these are dependent on the timing of the therapy in relation to delivery.76 Little is known about possible delayed effects of exposure to antineoplastic agents in utero. The major, primarily theoretical, concerns include physical and mental development, heart function, secondary malignancies, and infertility. In the prospective series of BCP patients reported by Berry et al.,33 there appeared to be no adverse impact on development in the children exposed to anthracycline-based chemotherapy in utero, although the impact on cardiac function and fertility was not or could not be assessed given the age of the children in the cohort. A large study with a median follow-up of 18.7 years of 84 children who were born to mothers who received chemotherapy during pregnancy for hematologic malignancies did not show any physical congenital abnormalities, nor any neurologic and psychological abnormalities, with the children demonstrating normal learning and educational behavior.77

It is difficult to extrapolate data from children who have received chemotherapy for leukemia because the amount and type of drugs given to a child with leukemia are different from those of the child exposed to chemotherapy in utero while the mother received treatment for breast carcinoma. With the limited data available, there does not appear to be significant long-term effects on the children of pregnant women exposed to chemotherapy in utero, especially second and third trimester exposures. However, this is an area requiring further study, especially in the children of BCP patients for whom the data are more limited. Women and their families should be cautioned that the data regarding long-term complications for the child have not been well defined.

Conclusions

  1. Top of page
  2. Abstract
  3. Epidemiology of Breast Carcinoma in Pregnancy
  4. Pathology
  5. Prognosis
  6. Methodology
  7. Diagnosis
  8. Treatment of Breast Carcinoma during Pregnancy
  9. Multidisciplinary Approach
  10. Monitoring of the Pregnancy
  11. Long-Term Implications for the Child
  12. Conclusions
  13. Acknowledgements
  14. REFERENCES

The initial assessment and management of women who have suspected BCP or lactation requires a multidisciplinary approach, with special attention to the use of appropriate investigations during diagnosis and staging. The treatment of the cancer needs to be carefully planned, with consideration given to the potential risks to the developing fetus. Pregnant women with breast carcinoma can be treated with anthracycline-based chemotherapy such as FAC in the second and third trimesters of pregnancy with minimal risk to the fetus. While breast surgery, mastectomy, or breast conservation can be performed with relative safety during pregnancy, patients who are clinically node-negative need to be counseled regarding the use of sentinel lymph node biopsy. Radiation therapy should be delayed until after delivery. The routine use of other systemic treatment such as the taxanes, trastuzumab, and tamoxifen is not recommended during pregnancy, given the limited data available.

In the treatment of the BCP patient, the evidence upon which we base our decisions has been largely limited to case reports, case–control studies and retrospective cohorts. Thus, it is critical that prospective data such as those collected at the University of Texas M.D. Anderson Cancer Center and the database of the German Breast Group/Breast International Group be continued.

REFERENCES

  1. Top of page
  2. Abstract
  3. Epidemiology of Breast Carcinoma in Pregnancy
  4. Pathology
  5. Prognosis
  6. Methodology
  7. Diagnosis
  8. Treatment of Breast Carcinoma during Pregnancy
  9. Multidisciplinary Approach
  10. Monitoring of the Pregnancy
  11. Long-Term Implications for the Child
  12. Conclusions
  13. Acknowledgements
  14. REFERENCES