Rosen's Breast Pathology, 4e

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Chapter 33

had a poorer survival (85%) at 10 years than women with non–pregnancy-associated breast carcinoma (93%), but the outcomes for both groups were favorable. 19 The same series reported a greater discrepancy in node-positive cases, with survival of 62% and 37% in the nonpregnant and pregnant groups, respectively. Others also found the prognosis of pregnancy-associated breast carcinoma to be relatively un­ favorable after adjustment for tumor size and nodal status. 45 The impact of subsequent pregnancy on prognosis in women previously treated for breast carcinoma remains un­ certain. 46 Most studies of this subject conducted retrospec­ tively appear to indicate that the prognosis for such patients is the same as or better than for patients who do not become pregnant. 47,48 Women who have received chemotherapy are generally advised to delay pregnancy for at least 6 months before attempting to conceive. 49 One case-control study compared 53 women who became pregnant after treat­ ment of breast carcinoma with a cohort without subsequent pregnancy, matched for stage of disease at diagnosis and a disease-free survival (DFS) at least as long as the interval to pregnancy in the study individual. 50 There were 5 deaths due to breast carcinoma among 53 women (9.6%) with subse­ quent pregnancies and 34 deaths among 265 controls (13%). The relative risk (RR) of death due to breast carcinoma in the subsequent pregnancy group was 0.8 (95% confidence interval [CI], 0.3 to 2.3), a result indicative of no increase in risk associated with subsequent pregnancy. A prospective study will be required to fully evaluate this issue, especially in the context of current management practices. An unusual complication of pregnancy concurrent with or subsequent to the diagnosis of breast carcinoma is the development of placental metastases. This is most likely to occur in women who have disseminated metastatic tu­ mors. 51–53 Gross evidence of metastatic carcinoma is usually apparent on the placental surface, and microscopic exami­ nation discloses tumor cells in the intervillous spaces, rarely with villous invasion (Fig. 33.1). The average age at diagnosis of patients with breast carci­ noma is in the mid-50s. The ages of the majority of affected women are within two decades above or below this mid­ point. Within this framework, the extremes of age may be considered younger than 35 years and older than 75 years. Breast carcinoma is widely thought to have a relatively poor prognosis in women younger than 35 years of age, whereas in those older than 75 it has been described as an indolent disease. Many published studies of this issue are not easily compared because of differences in defining age ex­ tremes or in the treatment that patients received. These are important considerations, especially when comparing data from the era when therapy consisted of surgery alone with recent data including neoadjuvant and adjuvant therapy, breast conservation, and radiation therapy. Data obtained BREAST CARCINOMA IN “YOUNGER” AND “OLDER” WOMEN

Prognostic Markers Estrogen receptors (ER) and progesterone receptors (PR) are significantly more often negative in carcinomas from pregnant and lactating women than in tumors from non­ pregnant age-matched controls. 16,19,22–26 A substantial pro­ portion of such carcinomas, ranging from 44% to 58%, are HER2-positive. 24–26 Treatment and Prognosis Although the primary treatment has generally been surgical, the use of adjuvant chemotherapy and breast conservation is an increasingly exercised option, depending on the circum­ stances in a particular case. 16 Surgery and chemotherapy are relatively safe treatment options after the fetal organogenesis period of the first 16 weeks has elapsed. Therapeutic irradia­ tion ought to be delayed until after completion of pregnancy. 27 However, the use of chemotherapy at any time during preg­ nancy has been linked to underdevelopment of placenta. 28 The most significant obstetrical outcome in women who have received chemotherapy during pregnancy is low birth weight. 29 Although no long-term complications have been reported in children whose mothers received chemotherapy for hematologic neoplastic diseases during pregnancy, the ­effects of fetal in utero exposure to maternal chemotherapy for breast carcinoma have not been well studied. 30 In the past, a modified radical mastectomy was performed in most cases for local control, in part to avoid radiation of the fetus during breast conservation therapy. 16,31–34 Radia­ tion should be delayed until after pregnancy. 16 Results in 9 patients treated by breast conservation in pregnancy were reported by Kuerer et al. 35 The patients were all stage I and stage II, with a median fetal gestation of 7 months. After a median follow-up of 24 months, there were no recurrences in the breast, although three women had distant recurrences. Thus far, no adverse effects have been reported with the use of either lymphoscintigraphy or methylene blue in preg­ nancy for the detection of sentinel lymph nodes (SLNs), 36–41 although the use of lymphoscintigraphy alone has been rec­ ommended in this setting. 16 In general, breast carcinoma in pregnancy can now be safely and effectively treated; how­ ever, management needs to be guided by duration of preg­ nancy and stage of breast cancer. 32 The overall prognosis of women with breast carcinoma diagnosed in pregnancy and lactation is relatively poor ow­ ing to the high proportion of patients with nodal metasta­ ses. 31,42 In one study, axillary nodal metastases were present in 74% of patients younger than 40 years of age with breast carcinoma diagnosed during pregnancy, whereas 37% of nonpregnant patients in the same age group had posi­ tive nodes. 43 When stratified by stage, some investigators reported no significant difference in outcomes between pregnancy-related and non–pregnancy-related patients of comparable age. 7,20,22,44 In a number of reports, 75% to 80% of node-negative patients remained alive or recurrence free with follow-up of 5 to 10 years. In one case-control study, node-negative women in the pregnancy and lactation group