Summary 'ee ;xamined the relationship between the frequency of premalignant lesions of the cervix and location of the transformation zone on the cervix among 8758 women as assessed using cervicography. An endo-and exocervical smear test was performed at the same time. Women with smear test classified CIN I or more were recalled and any abnormal area was biopsied under colposcopy. The transformation zone was located on the exocervix in 94% of women younger than 25 years old; as age increased, the proportion of women with a transformation zone located on the exocervix steadily decreased to reach less than 2% after 64 years old. As compared with women having a transformation zone in the endocervical canal, the age-adjusted likelihood of discovering a histologically proven dysplastic lesion was 1.8 times more frequent among women with a transformation zone located on the exocervix (95% confidence interval 1.1-2.9). This higher frequency seemed not attributable to a lower sensitivity of the smear test when the transformation zone was hidden. The results also showed that deliveries tended significantly to maintain the transformation zone on the exocervix. Parity is a known risk factor for cervix cancer, but the mechanism by which it favours malignant lesions remains unknown. Our results suggest that with increasing numbers of livebirths, the transformation zone is directly exposed for longer periods to external agents involved in dysplastic lesions.Keywords: dysplasia; parity; cervicography Most cancers of the cervix are squamous cell carcinomas originating in the transformation zone within which the junction between squamous and columnar epithelium is located. It has long been known that as age increases, the transformation zone becomes less accessible for cell sampling (Gondos et al., 1972 To explore differences in numbers of lesions detected according to the transformation zone status and to evaluate the influence of parity on the transformation zone status, we fitted logistic regression models using the GLIM software (Numerical Algorithms Group, Oxford, UK, 1977

Fewer endometrial abnormalities occurred during 2 years treatment with anastrozole compared with tamoxifen although statistical significance was not reached in this sub-protocol analysis.

Purpose: Here, we investigated the clinical relevance of an unprecedented combination of three biomarkers in triplenegative breast cancer (TNBC), both in human samples and in patient-derived xenografts of TNBC (PDX-TNBC): EGFR, its recently identified partner (MT4-MMP), and retinoblastoma protein (RB).Experimental Design: IHC analyses were conducted on human and PDX-TNBC samples to evaluate the production of the three biomarkers. The sensitivity of cancer cells expressing or not MT4-MMP to anti-EGFR (erlotinib) or anti-CDK4/6 inhibitor (palbociclib) was evaluated in vitro in 2D and 3D proliferation assays and in vivo using xenografts and PDX-TNBC displaying different RB, MT4-MMP, and EGFR status after single (erlotinib or palbociclib) or combined (erlotinib þ palbociclib) treatments.Results: EGFR and MT4-MMP were coexpressed in >70% of TNBC samples and PDX-TNBC, among which approximately 60% maintained RB expression. Notably, approximately 50% of all TNBC and PDX-TNBC expressed the three biomarkers. Single erlotinib and palbociclib treatments drastically reduced the in vitro proliferation of cells expressing EGFR and MT4-MMP when compared with control cells. Both TNBC xenografts and PDX expressing MT4-MMP, EGFR, and RB, but not PDX-TNBC with RB loss, were sensitive to erlotinib and palbociclib with an additive effect of combination therapy. Moreover, this combination was efficient in another PDX-TNBC expressing the three biomarkers and resistant to erlotinib alone.Conclusions: We defined a new association of three biomarkers (MT4-MMP/EGFR/RB) expressed together in 50% of TNBC and demonstrated its usefulness to predict the TNBC response to anti-EGFR and anti-CDK4/6 drugs used in single or combined therapy.

S_nmary The characteristics of cervicography and the Papamncolaou smear test have been compared for the detection of cervix lesions classified as CIN I or more. A total of 4,015 women were entered into the study. (IARC, 1986;Laara et al., 1987;Day, 1989).Cervicography as a means of screening was introduced by Stafl at the beginning of the 1980s (Stafl, 1981 Screening results qualified as 'atypical' or 'trivial change' were considered to be negative tests. CIN I lesions were considered to be low-grade lesions. CIN II or higher lesions were considered to be high-grade lesions. This distinction is based on the fact that there is a wide consensus that patients with CIN II or higher grade lesions should be subjected to further investigations, whereas the follow-up of CIN I lesions is still controversial (Ellman, 1991;Miller et al., 1991).The reference test was the histopathological examination of the biopsy specimens. All pathology slides were read by two pathologists, each unaware of the evaluation done by the other. In case of disagreement between the two readers, the final diagnosis was established by a senior pathologist aware of the two previous reports. (Morrison, 1985;Brecht & Robra, 1987; Shatzkin et al., 1987;Verbeek et al., 1991

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