Pregnancy and Breast Cancer

ABSTRACT & COMMENTARY

In one of the best episodes of "ER" last season, the wonderful actress, Lindsay Crouse (whose real-life husband is the great American playwright, David Mamet) portrays a pregnant physician who enters the emergency room in labor. A flood on the obstetrics floor has necessitated the conversion of the ER to a labor and delivery suite. In the course of evaluating her, Dr. Green inadvertently dislodges her wig and it becomes apparent that this pregnant patient is on chemotherapy. She then relates the history that she had had primary breast cancer a few years before that had returned as metastatic disease about eight months ago, at about the same time she discovered she was pregnant. She delayed the treatment of her cancer until the fifth month to assure that the baby would not be adversely affected by the cancer treatment. After an eventful labor, she delivers a healthy-appearing baby girl. As she holds her new baby, she begins to cry, overwhelmed with the great joy of holding her baby, for whom she had sacrificed a portion of her own life, and overwhelmed with great sadness, that she would be able to share so little of the baby’s life because of her disease. The complexity of feelings that Ms. Crouse conveyed in the act of crying was one of the most remarkable and touching performances I have ever seen; there certainly wasn’t a dry eye in my house. Even my teenage children were affected and they began to ask me about breast cancer and pregnancy.

I have seen women who had been treated for breast cancer have normal healthy babies after completion of treatment, but I have always discouraged women of child-bearing age who were being treated for breast cancer from becoming pregnant. I have a vague apprehension about the possible adverse effects of the many pregnancy-related hormonal and immunological changes on the growth of breast cancer cells. However, I know very few facts about the relationship. Recently, Malamos and colleagues examined the frequency of pregnancy among women with breast cancer under age 35 years. From three hospitals in Greece, they studied 243 women with breast cancer under age 35 years followed for a median of nearly three years; 21 (8%) became pregnant. Seven women had abortions and sixteen children were born to the remaining 14 patients. All the children were healthy and had normal development up through their age at the end of the study, which ranged from 12-142 months.

Breast cancer recurred in three of the patients who had become pregnant (14%); cancer recurred 0-31 months after pregnancy and one woman developed ovarian cancer five years after her pregnancy. Nineteen of the 21 patients who became pregnant had stage I or II disease at diagnosis; only two had stage III disease. The recurrence rate among the 222 women with breast cancer under age 35 who did not become pregnant was 39%, which was significantly greater than the recurrence rate for those who had become pregnant; however, there were more patients with stage III or IV disease at presentation among those who had not become pregnant. Thus, the data are not suggesting a protective effect from pregnancy. But, perhaps surprisingly, there is little evidence that pregnancy was harmful to the patients or augmented their risk of recurrence. The patients who became pregnant did so without, and in some cases against, their doctor’s advice, and two-thirds continued with their pregnancy despite their doctor’s warning that the recurrence risk might be increased. (Malamos, NA, et al. Oncology 1996;53:471-475.)

COMMENTARY

Fortunately, the concurrence of breast cancer and pregnancy is rare, occurring about once in 5000 pregnancies.1 The changes that occur in the breast during pregnancy may obscure the diagnosis in at least two ways: Either new masses are ignored or attributed to the physiological changes associated with pregnancy or a mass may actually seem to shrink as hormonal stimulation causes the breast tissue around the mass to enlarge. The resulting delay in diagnosis may be associated with the development of more advanced stage disease during pregnancy. Pregnant or lactating women have positive lymph nodes in 70-85% of cases,2,3 nearly twice as frequently as women as a group. However, stage for stage, it appears that breast cancer has the same natural history, whether the diagnosis is made during pregnancy or not. The concerns that the hormonal and immunological changes associated with pregnancy might accelerate tumor growth appear to be unfounded. Indeed, a recent study suggests that women who have had a pregnancy up to five years before the diagnosis have the same natural history as women who did not have a pregnancy in that interval.4 Thus, even the pregnancy-related changes occurring during a period in which preclinical breast cancer may be present seem to make no impact on the clinical course.

Any breast mass appearing in a pregnant woman should be evaluated similarly to a mass in a nonpregnant woman: mammography followed by biopsy, if indicated. If a diagnosis of breast cancer is made, management is certainly influenced by the pregnancy. Operable lesions in women without obvious axillary node enlargement may be treated with mastectomy and lymph node staging. If the lymph nodes are negative, it may be possible to carry the pregnancy to term without adversely affecting the prognosis. However, if the primary lesion is inoperable or the axillary lymph nodes are positive, most doctors would recommend termination of early pregnancies so that definitive treatment may be instituted as soon as possible. Late-term pregnancies may be carried on a few weeks until fetal viability is assured and then cesarean delivery followed by definitive treatment is usually recommended. Mid-trimester pregnancies pose a dilemma. In women who will not brook abortion, it is probably safe to administer a monthly combination chemotherapy regimen that omits methotrexate for 3-4 months until fetal viability is assured. Chemotherapy administered after organogenesis is surprisingly free of adverse effects on the fetus. Unlike some situations depicted on "ER" (for example, the high rate of successful cardiopulmonary resuscitation), the Lindsay Crouse cameo is highly plausible. The pregnant woman with metastatic breast cancer may well receive treatment and still deliver a healthy baby.

What do we advise our patients who have had definitive treatment for their breast cancer and remain fertile and eager for children? This situation makes me very nervous, but the data do not support my anxiety. The study highlighted above and others4 suggest that women with breast cancer who become pregnant do not increase their risk of disease recurrence. In fact, von Schoultz and colleagues4 also observed that women who became pregnant after a diagnosis of breast cancer had about half the risk of developing recurrent disease as women without a subsequent pregnancy. However, the numbers are small and the follow-up is short; and, while I am prepared to admit that my gut instincts about this situation may be wrong, I am not yet willing to say that pregnancy is therapeutic for breast cancer. But perhaps it is time to lighten up on women with breast cancer who wish to have (more) children.

References

1. Torres JE, Mickal A. Clin Obstet Gynecol 1975;18:219.

2. Holleb AI, Farrow JH. Surg Gynecol Obstet 1962;115:65.

3. Ribeiro GG, Palmer MK. Br Med J 1977;2:1524.

4. Von Shoultz E, et al. J Clin Oncol 1995;13:430.