Sunday, September 26, 2021

Breast Cancer in Pregnancy Case File

Posted By: Medical Group - 9/26/2021 Post Author : Medical Group Post Date : Sunday, September 26, 2021 Post Time : 9/26/2021
Breast Cancer in Pregnancy Case File
Eugene C. Toy, MD, Edward Yeomans, MD, Linda Fonseca, MD, Joseph M. Ernest, MD

Case 28
A 34-year-old G2P1001 Caucasian woman at 22 weeks’ gestation has noticed a painless lump in her right breast. She has no breast discharge and no family history of breast cancer. On examination, the patients has a 2.0 cm firm mobile mass of the right upper outer quadrant. There is no nipple retraction and no adenopathy. The left breast is unremarkable. The patient is referred to a breast center. The mass is noted to be solid on ultrasound examination, and the patient has a core needle biopsy of the mass revealing infiltrating intraductal carcinoma.

➤ What are the best options for therapy for this patient?
➤ What are the effects of chemotherapy on the pregnancy?
➤ What are the important considerations in managing her pregnancy?


ANSWERS TO CASE 28:
Breast Cancer in Pregnancy

Summary: A 34-year-old G2P1001 Caucasian female at 22 weeks’ gestation has 2 cm right breast mass, which on biopsy reveals an infiltrating intraductal carcinoma. There are no skin changes or adenopathy.

Best options for therapy: Because of the pregnancy and the size of the lesion, a breast conserving procedure would be difficult in this case since radiotherapy to the chest wall should not be used. Thus, mastectomy with axillary lymph node dissection is likely the best option.

Effects of chemotherapy on the pregnancy: Chemotherapy appears to be safe in pregnancy in the second and third trimesters.

Important considerations in managing her pregnancy: Excising the local lesion and lymph node sampling to properly stage the patient, followed by chemotherapy if nodes are positive for metastasis.


ANALYSIS
Objectives
  1. Be able to describe the clinical presentations of breast cancer, cervical cancer, and leukemia in pregnancy.
  2. Be able to describe the diagnostic approaches of breast cancer, cervical cancer, and leukemia in pregnancy.
  3. Be able to discuss the complications of management of each of the cancers described in the first objective in pregnancy.
  4. Describe the effect of pregnancy on the malignancies outlined in the first objective.

Considerations
The patient described this case has at least a stage II breast cancer and clearly needs therapy. At 22 weeks’ gestation, there is no option of waiting until delivery, since this delay would almost certainly affect the patient’s survival. Breast cancer therapy involves care of the local disease, dissection of the lymph nodes either by systematic dissection or sentinel node technique, and adjuvant therapy to prevent local recurrence. If this patient was not pregnant, then lumpectomy with sentinel node biopsy of the lymph nodes, and radiotherapy to the chest wall to help decrease recurrence to the chest would be standard therapy. Consideration should also be given to investigation of this patient for BRCA1 or BRCA2 mutations.


APPROACH TO
Malignancy in Pregnancy

Cervical cancer is the most frequent malignant neoplasm in pregnancy, followed by breast cancer and melanoma. The most common hematologic malignancy is Hodgkin lymphoma. The diagnosis of cancer in pregnancy can be delayed because of difficulties in distinguishing cancer-related symptoms from physiologic changes of pregnancy. Malignancy in pregnancy presents a significant dilemma in management as a result of conflict between maternal therapy and effects of treatment on fetal well-being. Due to the small number of cases and lack of large studies, there are no evidence-based guidelines to help with the management of pregnant patients with malignancies. The goal of cancer therapy in pregnant women is to provide the best cancer care for the patient while minimizing the potential harm to the fetus.1

Given the complex management involved in the care of a pregnant patient with cancer, a multidisciplinary team is essential to ensure that the mother, fetus, family, and all members of the health care team are well informed about the risks, benefits, and alternatives of the treatment choices and modalities. Management must be individualized to balance the ethical, moral, spiritual, and cultural issues that complicate such a diagnosis.

Breast Cancer
The definition of pregnancy-associated malignancy is breast cancer diagnosed during pregnancy or lactation up to 12 months postpartum. It is the second most common malignancy to complicate pregnancy. 

Diagnosis of breast cancer in pregnancy is usually delayed up to 5 to 7 months due to physiologic changes. Because of diagnostic delays, pregnant women are at higher risk of presenting late in disease in comparison to nonpregnant women.2 This is due to natural tenderness, engorgement, and increased nodularity of the breasts during pregnancy (see Table 28-1 for differential diagnosis). Stage for stage, however, the prognosis is the same as the nonpregnant woman. 

A breast lump discovered during pregnancy should be adequately and urgently assessed, preferably by a specialist breast team. The sensitivity of mammography decreases during pregnancy due to the increase in size, vascularity, and glandular density of the breast tissue. The sensitivity of mammography ranges from 63% to 78%.3 Adequate shielding is required during mammographic studies to decrease the radiation exposure to the fetus. Ultrasound has become the generally preferred imaging modality to evaluate a breast mass in pregnant women and may accurately differentiate between solid or cystic masses and is used as an adjunct to mammography. 

Core biopsy under ultrasound guidance remains the gold standard in making the diagnosis of a breast mass.1 When necessary, an open biopsy under local

Table 28–1 DIFFERENTIAL DIAGNOSIS OF BREAST MASS IN PREGNANCY OR LACTATING WOMEN

Breast cancer
Abscess
Lipoma
Lactating adenoma
Fibrocystic disease
Leukemia or lymphoma
Phyllodes tumor
Sarcoma



anesthesia is also appropriate. Clinically palpable lymph nodes should be evaluated by ultrasound-guided fine-needle aspiration (FNA) biopsy for pathology confirmation. Sentinel lymph node biopsy has not been fully evaluated in gestational breast cancer and is not recommended outside of clinical trials.4

Staging is according to the TMN system of the American Joint Committee on Cancer.1 Chest x-ray for staging with abdominal shielding is considered safe during pregnancy. MRI of the thorax is preferred over CT imaging. Radiologic staging is indicated for the evaluation of metastasis to the lung, liver, or bone if the patient is symptomatic, has palpable lymph nodes, or has T3 or T4 lesions. An abdominal ultrasound can be performed to evaluate the liver. Bony metastasis may be evaluated by low-dose bone scans or MRI without contrast of the thoracic and lumbar spine. 

Treatment of breast cancer in pregnancy is individualized according to the circumstances of each case: gestational age at diagnosis; surgical staging; surgical pathology of the tumor; hormonal receptor status; lymph node involvement; patient’s choice regarding child bearing.2 It is imperative that treatment is not delayed. Termination of pregnancy is usually not recommended but may be considered for an individual patient during treatment planning.1 Continuation of pregnancy represents no threat to the fetus and the risk of transplacental metastasis is extremely rare. 

Surgery is the definitive treatment for pregnancy-associated breast cancer.1 Mastectomy with axillary dissection is traditionally considered the best choice for stage I, II, and some stage III breast cancers.5 Axillary dissection is important for treatment and staging because nodal metastases are commonly found in pregnancy-associated breast cancer. 

In pregnancy, modified radical mastectomy with lymph node dissection is performed in place of breast conserving surgery to decrease the need of chemotherapy or radiotherapy. Stages III and IV are inoperable and are treated by simple mastectomy as a palliative measure, followed by chemotherapy,
hormone therapy, or radiotherapy.

Adjuvant chemotherapy is recommended in node-positive breast cancers or with tumors greater than 1 to 2 cm in diameter that are poorly differentiated. The most commonly used regimen in gestational breast cancer is doxorubicin with cyclophosphamide with or without 5-fluorouracil (FAC regimen).1 Chemotherapy agents can cross the placenta and have known effects in the first trimester. Therefore, chemotherapy is usually deferred in the first trimester as long as the health of the mother is not compromised. Reports are lacking on adverse pregnancy outcomes after exposure to cyclophosphamide, doxorubicin, and 5-fluorouracil during the second and third trimester.6 The use of tamoxifen in pregnancy has been contraindicated due to concerns over possible teratogenesis and its use for the treatment of hormone receptor-positive breast cancer is deferred until after delivery.7

In women less than 40 years, 30% will become amenorrheic and 90% of women over 40 years will cease menstruating following chemotherapy for breast cancer.2 In those who continue to ovulate and desire pregnancy, the recommendation is to wait 2 years following treatment of breast cancer, as the risk of recurrence is highest within the first 2 years after diagnosis.Nonhormonal methods should be used for contraception. Future pregnancy is safe unless the mother has an estrogen-receptor positive tumor and has not been in remission.

Women with pregnancy-associated breast cancer have the same survival stage for stage as nonpregnant women with breast cancer. They may do poorly, however, as an aggregate secondary to late diagnosis and aggressive disease.8

Cervical Cancer
Cervical cancer is the most common malignancy found in pregnancy. It most commonly presents as postcoital bleeding and a history of cervical dysplasia. Traditional signs and symptoms of early pregnancy overlap with the presenting complaints of invasive cervical cancer and can often be misinterpreted as threatened abortion.2 Therefore, it should always be one of the differential diagnoses with vaginal spotting or discharge and postcoital bleeding.

Colposcopy plays an important diagnostic role. The increased vascularity of the cervix in pregnancy, however, can make the interpretation of colposcopic findings difficult. The likelihood of a high-grade lesion progressing to invasive disease during pregnancy is low and treatment is not warranted during pregnancy due to the risks. Biopsy should be avoided if no invasive disease is suspected. If invasive disease is suspected, colposcopic-directed biopsies should be taken. This is associated with risk of bleeding, infection, or preterm labor. Endocervical curettage is contraindicated. Bleeding should be controlled with routine hemostatic methods. In the event of an unsatisfactory colposcopy examination, a repeat colposcopy evaluation is recommended in 6 to 12 weeks as the eversion of the transformation zone occurs during pregnancy.1

Cervical conization during gestation is reserved only for suspicion of invasive cancer.9 The safest time of doing a LEEP cone biopsy during pregnancy is during the middle second trimester, 14 to 20 weeks, or after fetal maturity has been documented. The procedure should be performed in the operating suite, with a knife, after the first trimester and after appropriate counseling about the risk of fetal loss and transfusion.

Invasive cervical cancer is clinically staged according to the International Federation of Gynecology and Obstetrics (FIGO). This involves clinical examination and chest x-ray with abdominal shielding. The use and timing of staging studies during pregnancy must be considered carefully because of the fetal exposure to ionizing radiation used with CT and fluoroscopy.

Pregnant women with cervical cancer are much more likely to have stage I disease and most have stage IB disease. Pregnancy does not affect the survival rate for cervical cancer.1 Women with stage IA1 cervical cancer can be followed with periodic colposcopy and cytology and delivery when obstetrically indicated.

Management of invasive cervical cancer in pregnancy is dependent on the gestational age at diagnosis, stage of disease, mother’s choice, and future childbearing desires. The choice of treatment modality for pregnant patients with cervical cancer is based on the same principles as those for nonpregnant patients. In general, vaginal delivery and reevaluation 6 weeks post-delivery is acceptable for those patients with stage microinvasive squamous cell carcinoma measuring 3 mm or less and without lymphovascular space involvement. With stage I disease (confined to the cervix), planned treatment delay, such as awaiting fetal lung maturity, is generally acceptable for those individuals whose pregnancies are greater than 20 weeks’ gestation. Patients with early-stage disease can be treated surgically with radical hysterectomy and bilateral lymphadenectomy. Depending on the time of diagnosis, surgery may be done early in gestation with termination of the pregnancy or delaying therapy until delivery.

When the cervical cancer is beyond stage I disease, and prior to fetal viability, primary chemoradiation is offered to the patient. If advanced disease is detected after fetal viability, a classical cesarean is performed with fetal lung maturity; this reduces the chances of blood loss and cutting into the tumor. Radiation therapy is used to treat advanced disease that is not amenable to surgery. In the first trimester, radiation usually leads to spontaneous miscarriage at a cumulative dose of 30 to 50 Gy.

For stage IB1 and IB2 cervical cancer in young patients, there is increasing evidence that radical trachelectomy allows for future pregnancy. Some limited studies indicate success with this modality.

Leukemia
The leukemias are a heterogenous group of malignancies that arise from genetically altered, lymphoid or myeloid progenitor cells, located in the bone marrow.10 This results in dysregulated growth and clonal expansion. Historically, the leukemias were classified into two basic groups: acute and chronic.

In pregnancy, most leukemias (90%) are classified as acute.10 Acute leukemia may be separated into several subtypes, on the basis of their cell of origin and cytogenetic abnormalities. The most common acute leukemia during pregnancy includes acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), and acute lymphoid leukemia (ALL).

The clinical manifestations of the acute leukemias are nonspecific and many of these symptoms are common in normal pregnancies, such as fatigue, weakness, dyspnea, and lack of energy. Patients may experience symptoms of epistaxis, easy bruisability, and recurrent infections. On physical examination, these patients often demonstrate pallor, petechiae, or ecchymosis.10 Patients present with elevated white blood cell counts, neutropenia, anemia, thrombocytopenia, disseminated intravascular coagulation with associated bleeding or thrombosis, and, occasionally, lymphadenopathy. The diagnosis of acute leukemia in pregnancy requires a peripheral blood smear demonstrating a normocytic, normochromic anemia with a mild to severe thrombocytopenia, and blasts are almost always present. Bone marrow biopsy with flow cytometry may also be performed for the diagnosis of acute leukemia.

In a patient with acute leukemia, the primary goal of chemotherapy is the eradication of leukemic clone cells from the bone marrow and restoration of normal hematopoiesis.10 Regardless of gestational age, the immediate induction of remission, as in the nonpregnant population, the immediate induction of remission remains the first objective in the management of the pregnant patient with acute leukemia. In a retrospective review of 37 women with acute leukemia during pregnancy, all cases were immediately started on chemotherapy, with therapeutic abortion recommended to the women presenting in the first trimester.11 Multiagent chemotherapy consisted of anthracycline and cytarabine, cyclophosphamide, prednisone, and asparaginase.

Fetal risk was highest with chemotherapy exposure in the first trimester; however, combination chemotherapy must be considered for acute leukemia patients who are pregnant because of the likelihood of rapid disease progression and maternal complications without therapy. Potential risks from acute leukemia and its treatment during pregnancy include preterm delivery, low birth weight, disseminated intravascular coagulation, and maternal or fetal bleeding and infection because of thrombocytopenia and neutropenia. It does not seem that the course of leukemia is adversely affected by pregnancy.12


Comprehension Questions

28.1 A 37-year-old woman at 8 weeks’ gestation is noted to have stage II breast cancer and she opts for radiotherapy. Which of the following statements is most accurate regarding this therapy?
A. Radiation leads to an all or none effect at this stage of pregnancy.
B. Typically miscarriage will not occur unless the radiation dose exceeds 30 Gy.
C. This patient’s prognosis is worse than a nonpregnant patient with a similar stage disease.
D. Chemotherapy in this patient is deferred until 20 weeks’ gestation.

28.2 What are the options for fertility-sparing procedure for stage IB cervical cancer and management of future pregnancy?
A. LEEP conization
B. Radical trachelectomy
C. Radical hysterectomy
D. Local pelvic irradiation

28.3 Which of the following statements is most accurate regarding performing colposcopy in the pregnant patient?
A. Unsatisfactory examinations are less commonly seen in the pregnant patient
B. The hormonal changes of pregnancy make colposcopy in pregnancy more challenging
C. The colposcopist should limit the biopsy to the least visible area
D. In general, visible lesions should be reevaluated with Pap smear or colposcopy about every 2 weeks.


ANSWERS

28.1 B. Usually miscarriage does not occur until the radiation dose exceeds 30 Gy. Chemotherapy is usually avoided in the first trimester, but considered acceptable in the second and third trimesters.

DOSE (Gy)

EFFECT ON FETUS

< 0.1

No major effect

0.1-0.15

Increased risk

2.5

Malformation in most

> 30

Miscarriage


Because there is no dose of diagnostic radiation that is completely safe for the fetus, radiography should be avoided if possible at all times during pregnancy. At all stages of gestation, radiation-induced noncancer health effects are not detectable for fetal doses below 5 cGy. At a dose of 5 to 50 cGy between 8 and 15 weeks after conception, growth retardation and mental retardation can occur. After 25 weeks, prenatal radiation exposure with doses higher than 50 cGy leads to fetal death in a dose-dependent manner.1 Therapeutic radiation for cervical cancer during pregnancy is lethal to a fetus.

28.2 B. Recent advances in surgical technique now allow patients with early invasive cervical cancer to maintain fertility. Radical trachelectomy with pelvic lymphadenectomy removes the tumor with adequate free margins, while retaining the uterine corpus for support of future pregnancies. This is possible for up to a small stage IB1 squamous cell tumor. The rate of first-trimester loss is the same as in the general population, but there is an increased rate of second-trimester loss. There is also an increased risk of preterm labor and the permanent cervical cerclage mandates cesarean delivery.13

Pelvic radiotherapy for cervical cancer leads to sterility as a result of the direct cytotoxic effect on the endometrium and ovarian injury.1

28.3 B. The challenge of performing an adequate colposcopic examination is related to pregnancy changes in the cervix: increased friability caused by related eversion of the columnar epithelium, cervical distortion from a low fetal presenting part, early effacement, and obstruction of visualization by the mucus plug.14

It is important that the health care provider performing the colposcopic examination be skilled in performing the test in pregnant women. An unsatisfactory colposcopy may be encountered in the early gestation, but a repeat colposcopy every 4 weeks or within 6 to 12 weeks may allow time for the migration of the transformation zone to the ectocervix, allowing a satisfactory examination.15


Clinical Pearls

See US Preventive Services Task Force Study Quality levels of evidence in Case 1
➤ Cervical cancer is the most common cancer in pregnancy (Level III).
➤ Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy or lactation up to 12 months postpartum (Level III).
➤ Ultrasound-guided core biopsy is the gold standard for diagnosis of breast cancer in pregnancy (Level II-3).
➤ Benefit to mother is balanced against risks to pregnancy (Level III).
➤ Multidisciplinary input involving obstetrician, gynecology oncologist, medical oncologist, radiologist, perinatologist, neonatologist, and support staff is very important (Level III).
➤ Tumor markers play a very limited role during pregnancy (Level II-3).
➤ Chemotherapy can be safely used, if needed, after the first trimester (Level II-3).
➤ Melanoma and hematologic malignancies are the commonest tumors that may metastasize to the placenta. Sporadic cases with fetal metastases have also been observed (Level III).

REFERENCES

1. Cohn D, Ramaswamy B, Blum K. Malignancy and pregnancy. In: Creasy and Resnik’s Maternal-Fetal Medicine: Principles and Practice. 6th ed. Philadelphia: Saunders, 2009. 2. Shah SA, Shafi MI. Cancer in pregnancy. Obstetrics, Gynaecology and Reproductive Medicine. 2008;18(10):279-284. 3. Ahn BY, Kim HH, Moon WK, et al. Pregnancy- and lactation-associated breast cancer: mammographic and sonographic findings. J Ultrasound Med. 2003;22:491-499. 4. Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph note biopsy in earlystage breast cancer. J Clin Oncol. 205;23:7703-7720. 5. Woo JC, Yu T, Hurd TC. Breast cancer in pregnancy: a literature review. Arch Surg. 2003;138:91-98. 6. 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. 7. Issacs RJ, Hunter W, Clark K. Tamoxifen as systemic treatment of advanced breast cancer during pregnancy—case report and literature review. Gynecol Oncol. 2001;80:405-408. 8. Leslie KK, Lange CA. Breast cancer and pregnancy. Obstet and Gynec Clin N Am. 2005;32:547-558. 9. Muller CY, Smith HO. Cervical neoplasia complicating pregnancy. Obstet Gynecol Clin N Am. 2005;32:533-546. 10. Hurley TJ, McKinell, JV, Irani MS. Hematologic malignancies in pregnancy. Obstet Gynecol Clin N Am. 2005;32:595-614. 11. Chelghoum Y, Vey N, Raffoux E, et al. Acute leukemia during pregnancy. Cancer. 2005;104:110-117. 12. Caligiuni MA, Mayer RJ. Pregnancy and leukemia. Semin Oncol. 1989;16:388-396. 13. Ramirez PT, Schmeler KM, Soliman PT, Frumovitz M. Fertility preservation in patients with early cervical cancer: radical trachelectomy. Gynecol Oncol. 2008;110(Suppl2):S25-S28. 14. Brown D, Berran P, Kaplan KJ, et al. Special situations: abnormal cervical cytology during pregnancy. Clin Obstet Gynecol. 2005;48:178-185. 15. Nguyen C, Montz FJ, Bristow RE. Management of stage I cervical cancer in pregnancy. Obstet Gynecol Surv. 2000;55:633-643.

0 comments:

Post a Comment

Note: Only a member of this blog may post a comment.