Adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers.

In order to better define the frequency and patterns of metastasis to the female genital tract, all cases of nonhematopoietic metastases to the adnexa, uterus, vagina, and vulva encountered in patients treated at Barnes Hospital between 1950 and 1981 were reviewed. Three hundred twenty‐five metastatic cancers from 269 patients were recovered. One hundred forty‐nine cases were from extragenital primaries; the remaining tumors were intragenital metastases. Ovary and vagina were the most frequent metastatic sites for both extragenital and genital primaries. The majority of the extragenital metastases were adenocarcinomas from the gastrointestinal tract, but a variety of other primaries did spread, on occasion, to the genital tract. Twenty‐seven percent of the metastases presented as possible primary gynecologic lesions, and 75% of these tumors had an extragenital origin. It is shown that despite certain trends in the distribution of metastases, all sites in the female genital tract are at risk for the occurrence of metastases.

Defective DNA mismatch repair in human tumors leads to genome-wide instability of microsatellite repeats and a molecular phenotype referred to as microsatellite instability (MSI). MSI has been reported in a variety of cancers and is a consistent feature of tumors from patients with hereditary non-polyposis colorectal cancer. Approximately 20% of cancers of the uterine endometrium, the fifth most common cancer of women world-wide, exhibit MSI. Although the frequency of MSI is higher in endometrial cancers than in any other common malignancy, the genetic basis of MSI in these tumors has remained elusive. We investigated the role that methylation of the MLH1 DNA mismatch repair gene plays in the genesis of MSI in a large series of sporadic endometrial cancers. The MLH1 promoter was methylated in 41 of 53 (77%) MSI-positive cancers investigated. In MSI-negative tumors on the other hand, there was evidence for limited methylation in only one of 11 tumors studied. Immunohistochemical investigation of a subset of the tumors revealed that methylation of the MLH1 promoter in MSI-positive tumors was associated with loss of MLH1 expression. Immunohistochemistry proved that two MSI-positive tumors lacking MLH1 methylation failed to express the MSH2 mismatch repair gene. Both of these cancers came from women who had family and medical histories suggestive of inherited cancer susceptibility. These observations suggest that epigenetic changes in the MLH1 locus account for MSI in most cases of sporadic endometrial cancers and provide additional evidence that the MSH2 gene may contribute substantially to inherited forms of endometrial cancer.

Specific histologic types of benign breast disease (BBD) may increase breast cancer risk. The authors analyzed data from a population‐based, case‐control study of women aged 20 to 54 with newly diagnosed breast cancer and control subjects randomly selected from the general population. A panel of pathologists classified the histologic findings of biopsy slides for 433 women with breast cancer and 261 control subjects, all of whom had a history of biopsy for BBD, as to the presence of epithelial hyperplasia, atypia, and other histologic features. When compared with women who had never had a breast biopsy, women with BBD without hyperplasia had an odds ratio of 1.5 (95% confidence limits [CL] 1.3 to 1.9), women with hyperplasia without atypia had an odds ratio of 1.8 (CL = 1.3, 2.4), and women with hyperplasia and atypia had an odds ratio of 2.6 (CL = 1.6, 4.1). Fibroadenoma was an independent risk factor for breast cancer (odds ratio = 1.7; CL = 1.1, 2.5). These findings suggest that women with BBD with epithelial hyperplasia either with or without atypia and women with fibroadenoma should be monitored carefully because of their elevated risk for breast cancer. Cancer 1992; 69:1408‐1414.

Purpose-To confirm that concurrent cisplatin (CT) with radiation therapy (RT) is associated with improved long-term progression-free survival (PFS) and overall survival (OS), compared to RT alone in stage IB bulky carcinoma of the cervix, when both groups' therapy is followed by hysterectomy.Methods-Three hundred seventy-four patients entered this trial. There were 369 evaluable patients; 186 were randomly allocated to receive RT alone and 183 to receive CT+RT. Radiation dosage was 45 Gray (Gy) in 20 fractions followed by low dose-rate intracavitary application(s) of 30 Gy to Point A. Chemotherapy consisted of intravenous cisplatin 40 mg/M 2 every week for up to six weekly cycles. Total extrafascial hysterectomy followed the completion of RT by six to eight weeks. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Results-Preliminary NIH Public Access Author ManuscriptAm J Obstet Gynecol. Author manuscript; available in PMC 2008 November 1. were well-balanced between the regimens. The median patient age was 41.5 years; 81% had squamous tumors; 59% were white. Median follow-up is now 101 months. The relative risk for progression was 0.61 favoring CT+RT (95% confidence interval [CI]: 0.43-0.85, p<0.004). At 72 months, 71% of patients receiving CT+RT were predicted to be alive and disease-free when adjusting age and for tumor size compared to 60% of those receiving RT alone. The adjusted death hazard ratio was 0.63 (95% CI: 0.43-0.91, p<0.015) favoring CT+RT. At 72 months, 78% of CT+RT patients were predicted to be alive, compared to 64% of RT patients. An increased rate of early hematologic and gastrointestinal toxicity was seen with CT+RT. There was no detectable difference in the frequency of late adverse events.Conclusion-Concurrent weekly cisplatin with RT significantly improves long term PFS and OS when compared to RT alone. Serious late effects were not increased. The inclusion of hysterectomy has been discontinued on the basis of another trial. Pending further trials, weekly cisplatin with radiation is the standard against which other regimens should be compared.