The most common malignancies associated with pregnancy are those of the breast, hematopoietic system, malignant melanoma, and genital tract (especially cervix). Specific questions to be considered when cancer is encountered during pregnancy are listed in Table 81-1. Although management of the pregnant woman with cancer is problematic, one basic tenet should be followed: A woman should not be penalized for being pregnant. Cancer therapy is discussed in greater detail in Chapter 57 of Williams Obstetrics, 23rd edition.
TABLE 81-1. General Considerations for Cancer Therapy during Pregnancy
The incidence of breast cancer varies with age of the population studied and averages 1 in 25,000 pregnancies. Pregnancy does not have a dramatic influence on the course of mammary cancer. However, hormonally induced physiological breast changes due to pregnancy tend to obscure breast masses. Survival in pregnant women is comparable with the rates expected with similar disease stages in nonpregnant women. Pregnant women with breast cancer have a 2.5-fold risk of metastatic disease compared with nonpregnant women.
Diagnosis and Treatment
Any suspicious breast mass found during pregnancy should prompt an aggressive plan to determine its cause, whether this involves ultrasound, fine-needle aspiration, or open biopsy. Ultrasound may be helpful in the initial evaluation of a palpable breast mass. Fine-needle aspiration is often the preferred procedure for definitive diagnosis of a suspicious breast mass, but has become less popular in the past few years because it has a higher insufficient tissue sample rate, and findings are difficult to interpret. Breast biopsy is usually reserved for masses in which fine-needle aspiration is not diagnostic. The dense breast tissue of pregnancy makes mammography less reliable. Magnetic resonance (MR) is more sensitive than mammography, but has a higher false-positive rate.
Once the breast malignancy is diagnosed, chest x-ray and a limited metastatic search are performed. Computerized tomographic bone and liver scans are probably contraindicated during pregnancy because of the ionizing radiation. Magnetic resonance imaging and ultrasonography are reasonable alternatives to assess for liver involvement.
Surgical treatment should not be delayed because of pregnancy. In the absence of metastatic disease, wide excision, modified radical mastectomy, or total mastectomy with axillary node staging can be performed. Breast-conserving surgery usually requires adjunctive radiotherapy, and this technique is usually not recommended unless the malignancy is diagnosed late in pregnancy. Radiotherapy is not recommended during pregnancy. Women with node-positive cancer should be given adjuvant chemotherapy without delay. Cyclophosphamide, doxorubicin, and 5-fluorouracil are currently recommended by most authorities.
Pregnancy Following Breast Cancer
There is little evidence to suggest that pregnancy after mastectomy for breast cancer adversely affects survival. Similarly, there are no data to suggest that lactation adversely affects the course of breast cancer. It seems reasonable to advise a delay in pregnancy for 2 to 3 years, which is the most critical observation period.
Hodgkin disease is the most common lymphoma encountered in women of child-bearing age. The most common finding is peripheral adenopathy, with neck and supraclavicular nodes commonly involved. Women may be asymptomatic or they may present with fever, night sweats, malaise, weight loss, and pruritus. Diagnosis is established by histological examination of involved nodes (Table 81-2).
TABLE 81-2. Ann Arbor Staging System for Hodgkin Disease
Treatment is individualized, depending upon the disease stage and pregnancy duration. Radiotherapy is normally preferable for isolated neck adenopathy and requires field modification to minimize fetal exposure. It is not recommended if the fields to be used will deliver significant radiation scatter to the fetus. Chemotherapy is a relatively safe option but is probably best avoided during the first trimester. Postponement of therapy until fetal maturity is achieved is considered reasonable by some if the diagnosis is made late in pregnancy. Because aggressive radiation and chemotherapy are often necessary to affect cure, pregnancy termination may be a reasonable option when the diagnosis of Hodgkin disease is made in the first half of pregnancy.
Most pregnant women with acute leukemia have pancytopenia. In three-fourths of women who develop acute leukemia during pregnancy, remission can usually be induced with chemotherapy. Survival has also improved for women with chronic myelogenous and lymphocytic leukemias. Perinatal outcomes are generally poor. Only 40 percent of pregnancies in women with acute leukemia result in live-born infants. Preterm delivery occurs in about 50 percent of women diagnosed during pregnancy.
In general, multiagent chemotherapy is given as soon as the diagnosis of leukemia is established, even if in the first trimester. There is no evidence that pregnancy has a deleterious effect on leukemia, and termination is not generally recommended to improve the prognosis. However, termination is a consideration in early pregnancy to avoid potential teratogenesis from chemotherapy. Significant pregnancy complications in women with active disease include infection and hemorrhage at the time of delivery. Vaginal delivery is preferable, and cesarean delivery is reserved for obstetrical indications.
Melanomas are relatively common in women of childbearing age. They are most common in light-skinned Caucasians, and over 90 percent originate in the skin from pigment-producing melanocytes in a preexisting nevus. There is no adverse effect on survival if melanoma is first diagnosed during pregnancy, or if a woman with previously recognized melanoma becomes pregnant.
Any suspicious alteration in a pigmented cutaneous lesion such as changes in contour, surface elevation, discoloration, itching, bleeding, or ulceration warrants a biopsy. Primary surgical treatment for melanoma is determined by the stage of the disease and includes wide local resection, sometimes with extensive regional lymph node dissection. Prophylactic chemotherapy or immunotherapy is usually avoided during pregnancy; however, chemotherapy for active disease is given if indicated.
Pregnancy provides an opportunity to screen for cervical neoplasia and premalignant disease. Cervical dysplasia is quite common (2 to 3 percent), with the incidence for carcinoma-in-situ during pregnancy about 1 per 1000 (Figure. 81-1).
Evaluation of the Pap smear can be more difficult during pregnancy. Conversely, colposcopic evaluation during pregnancy is easier to perform because the transformation zone is better exposed due to physiological eversion. Women with atypical squamous cells of undetermined significance (ASCUS) should be evaluated colposcopically if they test positive for high-risk human papillomavirus (HPV) DNA. If cytological changes of mild cervical intraepithelial neoplasia are confirmed, follow-up during pregnancy may also consist of colposcopic evaluation. In the absence of lesions detected by a satisfactory colposcopy, simply repeating the Pap smears later in pregnancy is usually adequate. Cytological changes that are suggestive of moderate or severe dysplasia or invasive disease require colposcopically directed biopsies to characterize the responsible lesion. Biopsy sites may actively bleed because of hyperemia, and this can usually be stopped easily with Monsel solution, silver nitrate, vaginal packing, or occasionally a suture. Women with histologically confirmed intraepithelial neoplasia may be allowed to deliver vaginally and given definitive treatment after delivery. There is regression postpartum in two-thirds of women with grades II and III intraepithelial neoplasia.
FIGURE 81-1 Frequency of reproductive-tract malignancies in 844 pregnant women. (Reproduced, with permission, from Cunningham FG, Leveno KJ, Bloom SL, et al (eds). Williams Obstetrics. 23rd ed. New York, NY: McGraw-Hill; 2010.)
To avoid risks of hemorrhage and membrane rupture, endocervical curettage is not done during pregnancy. Conization is also avoided because of an increased incidence of hemorrhage, abortion, and preterm labor. Cone biopsy is reserved for exclusion of invasive cancer.
Invasive Carcinoma of the Cervix
The extent of the tumor is more likely to be underestimated in the pregnant woman. Magnetic resonance imaging is a useful adjunct to ascertain extent of disease, including urinary tract involvement. Cystoscopy and sigmoidoscopy can be performed as necessary to rule out mucosal involvement.
Guidelines for treatment of microinvasive disease are similar to those for intraepithelial disease. Invasive cancer demands relatively prompt therapy. In general, with diagnosis during the first half of pregnancy, immediate treatment is advised. It is reasonable to await fetal maturity when diagnosis is made in the latter half of pregnancy. There is a growing experience with pregnancy following radical trachelectomy for fertility preservation in stages IB1 and IB2. And also with KTP laser conization in stage IA1 adenocarcinoma. The reader is referred to Chapter 57 of Williams Obstetrics, 23rd edition, for in-depth discussion of therapy for invasive cervical cancer during pregnancy.
Endometrial carcinoma is rarely associated with pregnancy.
Two-thirds of ovarian cancers found during pregnancy are of the common epithelial types. The rest are germ-cell tumors, and occasionally a stromal-cell tumor. Only about 5 percent of adnexal neoplasms diagnosed during pregnancy are malignant. Sonography is indicated for women in whom there is a palpable adnexal mass. It is helpful to differentiate functional cystic masses from solid or multiseptated masses. Evaluation of pelvic masses is discussed in detail in Chapter 40 of Williams Obstetrics, 23rd edition. The reader is referred to Chapter 57 of Williams Obstetrics, 23rd edition, for further discussion of the management of ovarian cancer during pregnancy.
Invasive squamous cell carcinoma of the vulva is only rarely associated with pregnancy. Vulvar intraepithelial neoplasia is seen more often in young women and is associated with human papillomavirus in most cases. Its potential for progression to invasive disease is unclear. A biopsy should be obtained of any suspicious vulvar lesion. Treatment of invasive disease is individualized according to the clinical stage and depth of invasion. Vaginal delivery is not contraindicated if the vulvar incisions are well healed.
For further reading in Williams Obstetrics, 23rd ed.,
see Chapter 57, “Neoplastic Diseases.”