Breast Cancer and Pregnancy

Barry Flynn, M.D., B.S.

William D. Kaplan, M.D.

January 6, 1986

Case Presentation:

A 29 year-old woman noted an upper outer quadrant mass in her left breast in June of 1986. In July she had a positive pregnancy test; at her first obstetric appointment in September, she was referred for a surgical opinion of the breast mass. After an unsuccessful attempt at needle biopsy, she underwent excisional biopsy on 11/4/86, which revealed an infiltrating ductal carcinoma with tumor at the margins of resection; 5/17 axillary lymph nodes were positive for tumor. Flow cytometry on the tumor was reported as aneuploid, with high S phase, indicating increased risk of relapse with poor survival probability. Estrogen and progesterone receptor levels were < 3 and 5 fmol/mg, respectively. At the time, the patient was 23 weeks pregnant.

Findings:

The patient had a normal chest X-ray (with fetal shielding) and a normal Tc-99m MDP bone scintigram (5 mCi injected dose).

In light of her poor prognosis termination of the pregnancy was discussed with the patient and her husband. This option was declined by the parents and accordingly, mastectomy for local disease control was arranged with chemotherapy to commence after term fetal delivery.

Discussion:

Approximately 3% of breast cancers are associated with pregnancy or lactation. Prognosis was previously thought to be much worse than for non-pregnant patients. It is probably approximately the same as for pre-menopausal women of the same stage; there may be a higher number of node positive presentations in the pregnant group, however. Some studies have shown a worse outcome when treatment is initiated in the second half of pregnancy as compared with the first half or during lactation. Recent data do not confirm this, however.

Theoretical considerations for why pregnancy could be associated with more severe disease include: (a) increased level of circulating stimulatory hormones, (b) delay in diagnosis, (c) expanded extra-vascular and lymphatic capacity in the engorged breast, and (d) a relative maternal immuno-incompetence.

No studies have demonstrated a therapeutic role for abortion in altering the natural history of the disease. Biopsy and mastectomy can be well tolerated by mother and fetus with the risk of spontaneous abortion following general anesthesia only approximately 1%.

Chemotherapy has not been shown to cause congenital malformations when given in the second half of pregnancy. Due to the risk of thrombocytopenia, it should be avoided in the peripartum period. In a study involving 163 patients given chemotherapy in the first trimester there were 19 cases of fetal malformations (10.4%). However, 10 of these cases involved Aminopterin, an agent formerly used to induce abortion. Of the remaining 9 cases (5%), three woman had received radiation therapy during the first trimester and a fourth had radiation therapy just prior to pregnancy. Four of the women who produced malformed infants had also received chemotherapy prior to conception. Chemotherapy given during the second and third trimester did not increase the risk of teratogenesis.

The dose of Tc-99m MDP administered to this patient was reduced to 5 mCi. This would deliver approximately 1.3-1.8 mGy (125-180 mREM) to the fetus, assuming a constant maternal urinary bladder volume of 200 ml. This patient was encouraged to void frequently. Irradiation of the fetus below 50 mGy has not been observed to cause congenital malformations or growth retardation. The single exception is one report of ocular abnormalities at low absorbed doses. This finding is at variance with a massive amount of experimental and epidemologic literature.

At absorbed doses of 100 mGy, the risk of spontaneous abortion very early in pregnancy appears to be increased by 0.1-1%. If a linear extrapolation were valid then 10 mGy may increase the spontaneous abortion rate by 0.01-0.1%.

References:

1) Medical effects of ionizing radiation. FA Mettler, RD Mosley (eds), Grune and Stratton, Inc. 1985.

2) Simon JD. Update recommendations for pregnant women. JNM, December 1986.

3) McGuire WL, Dressler LG. The emerging impact of flow cytometry in predicting recurrence and survival in breast cancer: a review. J Nat Can Instit, 75.

4) Wallace CJ. Current problems in cancer. Vol VII, No. 9, March 1983.

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J. Anthony Parker, MD PhD, jap@nucmed.bih.harvard.edu