Breast cancer during pregnancy: quantifying the risk of treatment delay

312

Citations from the literature /International Journal of Gynecology & Obstetrics 54 (19%) 307-316

relate to the more favorable prognosis of this subset of tumors in comparison to other gynecologic tumors containing mutated p53 genes. hnl0pwnt-d lmmMwarlao~

cllamdm~ofaninte~~r tmoorvocclwoatexprwslogatojor

btmmpatlMuty complexSantin A.D.; Ioli G.R.; Hiserodt J.C.; Marietta A.; Pecorelli S.; DiSaia P.J.; Granger G.A. USA AM J OBSTET GYNECOL 19% 174/2(633-640) Objective. We initiated studies to develop cytokine-secreting human ovarian carcinoma cells for the purpose of using these cells as vaccinesfor the treatment of advanced epithelial ovarian cancer. Study design. A human ovarian carcinoma cell line (UCI-107) was genetically engineered to secrete the cytokine interleukin-2 by retroviral-mediated gene transduction. Results. One clone, termed UCI-107A IL2 AS, constitutively secretedhigh levels of interleukin-2 (i.e. 2000-2300 pg/ml per lo5 cells per 48 h) for >55 passagesand 8 months of study. Unlike parental- and vector-transduced cells, UCI-107A IL-2 AS cells were aneuploid and failed to express major histccompatibility complex class-l and HER2/neu surface. antigens. UCI-107A IL2 AS cells were highly resistant to killing by gamma-irradiation and continued to produce high levels of interleukin-2 even after irradiation with 10000 cGy. Balb/C nude mice injected intraperitoneally with UCI-107A IL-2 AS cells survived significantly longer than control animals, with 25% of the animals totally rejecting their tumors. UCI-107A IL2 AS was totally resistant to killing by fresh allogeneic peripheral blood lymphocytes in 4-h chromium-51 release assaysbut induced high levels of killing in 72-h long-term cytotoxic assays.Conclusion. The potential useof theseinterleukin2-secretingovarian carcinoma cells as vaccines for women with advanced ovarian cancer will be discussed. Breast emus tJm& pregmacy: quntIfyIng UserIak of treatment *Y Nettleton J.; Long J.; Kuban D.; Wu R.; Shaeffer J.; El-Mahdi A. USA OBSTET GYNECOL 19968713(414-418) Objective. To quantify the risk of axillary nodal metastases due to delayed treatment of breast cancer during pregnancy. Methods. A mathematical model using recently published data was developed to correlate primary breast tumor size with the percentage of pathologically positive axillary lymph nodes. Using this relationship obtained from pathologic data and the accePted relationship of tumor growth and time, Y, = Yte((lnZ)niDT), an equation estimating the increasedrisk of axillary metastasesdue to each day of treatment delay was derived: AX = 3.7 n/DT, where X = percent positive axillary lymph nodes, n = number of days’ delay in treatment and DT = tumor doubling time. Results. A l-month delay in treatment for an early-stage primary breast cancer with a 13O-day doubling time increasesthe risk of axillary lymph node involvement by 0.9%. A 3-month delay increasesthe risk by 2.6% and

a Cmonth delay by 5.1%. For breast cancer with a 65day doubling time, a l-month delay increasesthe risk by 1.8%,a 3month delay by 5.2% and a &month delay by 10.2%.Conclusion. Axillary lymph nodes are the most important prognostic indicator for survival in breast cancer.Our mathematical model ~uggcststhe daily increased risk of axillary metastasesdue to treatment delay is 0.028%for tumors with moderate doubling times of 130days and 0.057%for tumors with rapid doubling times of 65 days. This minimal maternal risk may be acceptable to some third trimester pregnant women with early breast cancer who prefer organ-sparing treatment with radiation after delivery to a mastectomyduring pregnancy. This model further quantitates the increased risk of mortality borne by pregnant women whose breast cancer diagnosis is delayed. HIV INFECTIONS Neonatal clumW&s lo rapidly progmdve peri~taUy PC@OdHlV-IdkOtiS Mayaux M.-J.; Burgard M.; Teglas J.-P.; Cottalorda J.; Krivine A.; Simon F.; Puel J.; Tamalet C.; Dormont D.; Masqueher B.; Dot&n A.; Rouxioux C.; Blanche S. FRA J AM MED ASSGC 1996275/8 (606-610) Objective. To identify clinical and laboratory parameters at birth that are associatedwith the rapidly progressive form of HIV-I disease in children born to infected mothers. Design. Multicenter, prospective study of infants born to HIVseropositive mothers. Setting. A total of 62 obstetric and pediatric centersin France. Participants. Gf 1386children born to HIV-1-seropositive mothers at least 18 months before the cut-off date, 267 were infected. Infection was defined as serological positivity at 18 months or death from HIV disease before this age. Main outcome measure.Category C events (including opportunistic infections, recurrent severe bacterial infections, cancers, specific enccphalopathy and wasting syndrome) in the new pediatric Centers for Disease Control and Prevention class.iBcationduring the first year of life, according to clinical, immunological and virological findings at birth. Results. The risk of category C manifestations at 12 months was significantly higher when an infected newborn had liver and/or spleen enlargement and/or adenopathies (38.1 vs. 15.1%;relative risk [RR] 2.5; 95% C.I. 1.4-6.0; P < 0.02) or a low proportion (<30%) of CD4+ cells at birth (45.5 vs. 15.oo/o; RR 3.0; 95%C.I. 1.4-6.4; P < 0.005).Similarly, HIV-I culture and/or polymerase chain reaction positivity during the first week of life was associatedwith a higher risk of the early, severeform of HIV infection (26.4 vs. 9.3%; RR 2.8; 95% C.I. 1.3-6.1; P < 0.006). In case of positive antigenemia at birth, the risk was 50.0 vs. 14.4%(RR 3.5; 95% C.I. 1.9-6.2; P < 0.001).Theseparameters,determined at birth, were strongly interrelated and could reflect active diseaseonset in utero in some casesof early, severeHIV-l diseasein childhood. Conclusions. Theseprognostic markers, particularly virological parameters, are of value in monitoring children infected by HIV and might serve as a basis for early therapeutic intervention.