The association of microsomal epoxide hydrolase polymorphisms and lung cancer risk in African-Americans and Mexican-Americans.

This study evaluated the influence of genetic polymorphisms in the microsomal epoxide hydrolase (mEPHX) gene on lung cancer risk in a case-control study of two different ethnic groups, Mexican-Americans and African-Americans. There were 138 lung cancer cases (60 Mexican-American and 78 African-American) and 148 controls (76 Mexican-American and 72 African-American). There was a significant difference in the distribution of the mEPHX exon 4 polymorphism between the two ethnic groups with African-Americans more likely to be heterozygous and Mexican-Americans to be wild-type. There was no significant difference between the ethnic groups for the allelic distribution of the mEPHX exon 3 polymorphism. When the exon 4 and exon 3 polymorphism distributions in cases and controls were examined by ethnicity, only the Mexican-American cases showed a substantial proportion with the exon 4 polymorphism. The exon 4 polymorphism was associated with a significantly increased risk of lung cancer only among the Mexican-American cases (adjusted OR 3.6, 95% CI 1.26, 10.42). Younger Mexican-Americans with the exon 4 polymorphism had a greater risk of lung cancer than older members of their groups (adjusted OR 7.4, 95% CI 1.36, 40.23; 1.6, 95% CI 0.33, 7.80, respectively). The exon 3 polymorphism did not appear to significantly increase the risk of lung cancer in all but one study group examined. Mexican-Americans younger than 65 years did demonstrate an elevated risk of lung cancer (adjusted OR 4.6, 95% CI 1.19, 17.56). However, no statistically significant risk was observed in the African-American study groups for both exon 3 and exon 4 polymorphisms. These findings suggest that the presence of the exon 4 and exon 3 polymorphisms of mEPHX may be associated with an increased risk of lung cancer particularly among younger Mexican-Americans in this study.

Breast cancer during pregnancy.

The care of a pregnant breast cancer patient is a challenging clinical situation that historically has placed the welfare of the mother in conflict with that of the fetus. For the woman in this situation, the emotions usually associated with pregnancy can be overshadowed by the emotions aroused by a diagnosis of breast cancer and its subsequent treatment. The majority of published information on the management of breast cancer during pregnancy has consisted of retrospective chart reviews, case reports, and anecdotes. There is a paucity of published data from the prospective study of women who are pregnant at the time of their breast cancer diagnosis. This review will endeavor to address the diagnosis, staging, and subsequent treatment of breast cancer during pregnancy. The limited information available for this group of women on the outcomes of labor, delivery, and neonatal health will also be reviewed. This review will not specifically address pregnancy that occurs after diagnosis and subsequent treatment for breast cancer. However, some data, particularly those of an epidemiologic nature, address breast cancer diagnosed during pregnancy or within the year following delivery.

Breast cancer during pregnancy.

The concurrent diagnosis of breast cancer and pregnancy is a challenging clinical situation that historically has placed the welfare of the mother in conflict with that of the fetus. Modified radical mastectomy, the preferred surgical option in women with breast cancer during pregnancy, can be accomplished with minimal fetal risk. Although breast-conserving surgery (lumpectomy or quadrantectomy) can be performed, the radiation therapy required to complete local therapy for the breast must be delayed until after delivery because of the risks associated with fetal exposure to radiation. Although much of the literature on the pharmacologic treatment of breast cancer during pregnancy is anecdotal, recently published data from our institution support the premise that breast cancer can be treated safely during the second and third trimesters of pregnancy with combination chemotherapy consisting of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). Therapeutic abortion does not appear to improve survival for the mother, but it may be an option if maternal health is jeopardized or fetal anomalies are seen or suspected.

Current perspectives on aromatase inhibitors in breast cancer.

PURPOSE AND DESIGN: One way to deprive hormone-dependent breast cancer of estrogen is to prevent its synthesis. This is achievable by inhibiting the aromatase cytochrome P-450 (P-450arom) enzyme complex responsible for the ultimate step in estrogen production. A new generation of specific and selective aromatase inhibitors is currently under investigation. The purpose of this review is to outline the preclinical test systems for screening these inhibitors, to summarize the preclinical and clinical data published to date, and to discuss the future application of these inhibitors in the management of breast cancer. RESULTS AND CONCLUSION: Disadvantages to the use of earlier inhibitors are described. In vitro and in vivo experiments that reflect the potency and selectivity of new inhibitors are highlighted. From preliminary clinical trials, these inhibitors appear to have excellent pharmacokinetic profiles and produce few side effects when administered orally. Activity against postmenopausal metastatic breast cancer has been demonstrated for the agents reviewed. They are all now in phase III testing to determine their relative efficacy in this setting. Their application in combination with both hormone therapy and chemotherapy, in premenopausal metastatic disease, and in the adjuvant setting in both premenopausal and postmenopausal women remains to be defined.