Diagnosing and Managing Breast Disease During Pregnancy and Lactation

, University of Iowa College of Medicine

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In This Article

Pregnancy-Associated Breast Cancer

Incidence. Carcinoma of the breast complicates 1 in 3000 deliveries in the US. The incidence of this malignancy during pregnancy is exceeded only by carcinoma of the uterine cervix; together, the 2 malignancies account for 25% of cancers diagnosed during pregnancy.[27] Pregnancy-associated breast cancer (PABC) is defined as cancer diagnosed during pregnancy or within 1 year of delivery.

Mathematical analysis has demonstrated that the incidence of PABC is about what one would expect by chance. When the probable preclinical latent period of breast cancer is considered, it becomes likely that even larger numbers of young women with breast cancer have been pregnant during the course of their disease, although they do not meet the definition of PABC. The incidence of PABC is expected to increase as large numbers of women in developed countries defer childbearing into their 30s and 40s. The incidences of a significant positive family history and of bilateral disease appear to be the same as those in the general breast cancer population, and studies of BRCA-1 and other tumor markers in PABC have not yet been reported.

Although it has been postulated that the complex hormonal changes and immunologic alterations associated with pregnancy might create a climate favorable to cancer growth, definitive evidence in favor of this hypothesis is lacking.[28,29] An initial clinical impression that PABC was especially virulent has given way, gradually, to the concept that survival is equivalent to that observed in age- and stage-matched women who are not pregnant.[30,31,32] Some recent data, however, suggest that a subset of women who develop PABC may indeed fare worse than their nonpregnant counterparts.[33,34,35]

Presentation and evaluation. Most PABC presents as a painless mass, which in 90% of cases is discovered by the patient herself. Many series have documented significant delay in diagnosis (averaging 5 to 7 months, but as long as 18 months), with the responsibility for this delay ascribed to both patient and physician.[36,37,38] Difficulty in palpating masses within the engorged and enlarged breasts, a tendency to attribute a mass to inflammation or mastitis, inadequate follow-up by the physician or patient, and reluctance to biopsy a questionable mass may all be involved.

Such delaying factors have been cited as being responsible for the observed tendency toward more advanced disease at time of diagnosis (larger tumors, a higher percentage with positive axillary nodes), but a different biologic behavior also may be involved. As with all breast cancer patients, an occasional patient with PABC has extensive metastatic disease at the time of initial diagnosis, and sometimes the primary tumor within the breast is occult.

As already mentioned, a large variety of benign processes can occur and present as breast masses. If an aggressive biopsy policy is followed, a large percentage of all masses biopsied are benign. Greater use of FNAC is an alternative way to evaluate mass lesions and should be used rather than sequential examination. The decision to simply follow a breast mass in a pregnant woman not only introduces additional delay and the possibility of inadequate follow-up, but is also prone to failure because the continuing enlargement of the breasts renders clinical breast examination even more difficult and may create the false impression that a mass has disappeared. Therefore, any pregnant patient with a suspicious mass should be referred to a surgeon for evaluation by FNAC or biopsy.

Mammography is not particularly useful. The radiodense nature of the breast tissue in pregnant and lactating women significantly decreases the sensitivity of this examination.[37,39,40] Since most patients with PABC present with a palpable mass, the role of imaging modalities is limited to excluding other lesions. Ultrasound is emerging as an increasingly useful diagnostic tool, particularly in confirming the presence of borderline-palpable masses in PABC.[39,40] As with any patient with a breast mass, imaging modalities do not unequivocally identify the nature of the lesion, and histologic confirmation is necessary before one can conclude that a given mass is benign or malignant.

FNAC was successful in predicting the benign versus malignant nature of 214 mass lesions during pregnancy (with 9 carcinomas, all diagnosed as either carcinoma or suspicious) in one series.[41] Similar findings in other studies have involved smaller numbers of cases.[42,43,44,45] It is important to keep in mind that because the changes in pregnancy can complicate the cytologic examination of FNAC, the cytopathologist must be advised of the stage of pregnancy and must be familiar with the cytologic appearance of benign lesions under the influence of pregnancy.

When necessary, breast biopsy may be performed under local or general anesthesia with minimal risk to the fetus.[46,47] The overwhelming number of lesions in all series of breast biopsies and FNACs performed during pregnancy are benign. If clinicians use FNAC as the initial procedure to rule out malignancy, this strategy may increase the yield rate when biopsy is required and decrease the delay in diagnosis.

Biopsy also may be performed during lactation if needed. The major risks of infection and milk fistula can be minimized if the woman ceases breast-feeding at least 48 hours prior to biopsy. If the woman wishes to continue breast-feeding, she should empty the breast the morning of the biopsy.

Biopsy during pregnancy and lactation requires meticulous technique and special attention to hemostasis. Local anesthesia may be difficult or impractical in the engorged and enlarged breasts. Thus, while local anesthesia has the obvious appeal of minimizing risk to the fetus, some surgeons may prefer to use general anesthesia to ensure more control of conditions during the biopsy.

Histology. The histologic types of breast cancer diagnosed during pregnancy and lactation are similar to those seen in the general population of breast cancer patients. Inflammatory carcinoma, once thought to be more commonly seen in PABC, is now thought to occur at about the same rate as it does in nonpregnant women of the same age. Metastatic tumors, Hodgkin's disease, non-Hodgkin's lymphomas, Burkitt's lymphoma, and sarcomas also occur.

Most PABC is estrogen- and progesterone-receptor (ER/PgR) negative. The standard ligand-binding assay used in most laboratories may yield a false-negative result in the estrogen- and progesterone-rich milieu of PABC, and special techniques have been advocated to increase the yield.[48,49] However, it is likely that many tumors in PABC are ER/PgR negative because they fall into the subset of aggressive, poorly differentiated breast cancers that are more commonly seen in younger women--regardless of pregnancy status--as compared with the entire population of breast-cancer patients. Therefore, the ultimate comparison of prognosis, stage-for-stage and age-matched, may be similar.

Treatment. The general philosophy of treatment today is best summarized as follows: Treat the cancer, and allow the pregnancy to proceed. Pregnancy termination, once advocated routinely because of fear that the hormonal and immunologic milieu would adversely affect patient survival, is now rare. Special circumstances may arise in which termination of pregnancy might be advocated; for example, an advanced and hormonally sensitive tumor diagnosed early in pregnancy, or a tumor that advances rapidly during pregnancy. Treatment must be individualized, and each patient's case requires a team approach involving a surgeon and an obstetrician.[27,50,51]

Most surgeons continue to advocate modified radical mastectomy for PABC. Breast-conservation therapy (lumpectomy and radiation therapy, with or without axillary node sampling) has no proven benefit in this setting. Radiation therapy is impracticable during pregnancy because even with abdominal shielding, the fetal dose is high. The use of lumpectomy followed by chemotherapy, with radiation therapy delayed until after delivery, is unproven in this setting.[51]

Metastatic work-up is performed selectively, and tests are limited to situations in which therapeutic decisions require documentation owing to a high suspicion of metastatic disease. A chest x-ray (with abdominal shielding) can be performed with minimal radiation exposure to the fetus. Ultrasound of the liver is useful for excluding liver metastases; the alkaline phosphatase is generally elevated in pregnancy and is not a reliable indicator. Magnetic resonance imaging is an alternative technique that has been used in pregnancy. Bone scan can be performed with appropriate precautions, but the yield is low.

Chemotherapy can be given during pregnancy if agents are carefully selected.[52,53,54,55] The risks include toxic drug effects that cause teratogenicity and fetal growth retardation, as well as complications of bleeding or infection should unplanned premature delivery occur during a chemotherapy nadir. It is conceptually helpful to differentiate situations in which cure is possible from those in which chemotherapy is given for purely palliative purposes. In the latter circumstance, the goal shifts to protection of the fetus. Delaying chemotherapy until after delivery provides the best protection for the fetus but may do so at the expense of controlling maternal disease. Although breast cancer treatment during lactation is still highly controversial, the full range of therapeutic modalities is available. Breast-feeding during chemotherapy, however, is contraindicated because of potential harm to the infant, since the drugs can reach significant concentrations in the breast milk.[56]

Prognosis. Stage for stage, most research suggests that survival of women with PABC is equivalent to that of age-matched nonpregnant controls.[32,36] To date, just one study has concluded that patients with PABC may fare worse.[34] It is unknown whether the findings in this study reflect more aggressive biologic behavior of the neoplasm, the altered host milieu of pregnancy, or simply the poor outcome that has been noted in other studies among young women who develop breast cancer. It has also been suggested that the poor outcome noted in this latter group is related to pregnancy that began during the preclinical (latent) phase of the tumor. It is important to note that the definition of PABC is a purely artificial one. Undoubtedly, there are many young women who are pregnant during the development of their breast cancer who do not fit the definition of diagnosis during or within 1 year of pregnancy, but whose earlier pregnancy may have played a role in tumor development.

Metastatic spread of breast cancer to the placenta has been described, but fetal transmission has never been documented in PABC (unlike melanoma, which can be transmitted). Careful examination of the placenta at delivery is advocated, including histologic examination of the intervillous spaces. Placental spread is usually associated with metastatic disease in the mother.[51]

Significant emotional issues surround care of women with PABC. Multiple physicians from different specialties are involved in patient management, and a team approach that includes psychologic support is essential.[57,58]

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