Michel Coibion

Transformation zone location and intraepithelial neoplasia of the cervix uteri

We examined 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 remain 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.

Endometrial disorders in 406 breast cancer patients on tamoxifen: the case for less intensive monitoring

OBJECTIVES To describe the endometrial appearance in postmenopausal breast cancer patients on tamoxifen and to assess a routine surveillance scheme for endometrial lesions. STUDY DESIGN Three hundred and seventeen postmenopausal breast cancer women already on tamoxifen at the start of the study (group I) and 89 breast cancer women assessed before any tamoxifen intake (group II) underwent an initial and then yearly scans with transvaginal ultrasonography, followed by an hysteroscopy and biopsy for women with an endometrium thickened above 8mm. Endometrial thickness was also measured in 823 women with no breast cancer nor tamoxifen intake (group III). RESULTS Initial mean endometrial thickness was 8.2mm in group I, 4.4mm in group II and 3.4mm in group III (P<0.001). Eighteen percent endometrial lesions were found in group I and 3.3% in group II. We observed a significant association between endometrial pathology and both cumulated dose and total duration. Polyps were the most frequent and first to appear pathology. Five cancers were detected in group I, and all of them had taken tamoxifen for more than 3 years. CONCLUSION Our surveillance scheme could be lightened; an acceptable screening scheme might include a baseline assessment before the start of tamoxifen and, if normal, yearly screening after 3 years of tamoxifen therapy, yearly surveillance for women with an abnormal baseline assessment and immediate investigation for symptomatic women.

Is there a role for cervicography in the detection of premalignant lesions of the cervix uteri

The characteristics of cervicography and the Papanicolaou 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. The sensitivity of cervicography is significantly higher (McNemar test, P < 0.0001), but its specificity remains significantly lower (McNemar test, P < 0.0001), and its higher sensitivity does not apply to lesions classified as CIN II or more (high-grade lesions). Hence, if patients with a positive screen result are to be referred for colposcopy-biopsy, cervicography is not a suitable alternative to the smear test for the screening of cervical cancer. However, cervicography can be envisaged as a complementary tool to the smear test because of (a) its higher capability to detect high-grade lesions among women less than 35 years old and (b) its potential superiority in following low-grade lesions. It may also serve as a tool for quality assurance audit of the smear test.

The ATAC adjuvant breast cancer trial in postmenopausal women: Baseline endometrial subprotocol data

Objective The ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial is a randomised, double‐blind trial comparing ‘Arimidex’ (anastrozole), alone or in combination with tamoxifen, relative to tamoxifen alone as a five year adjuvant treatment for postmenopausal women with early breast cancer. Because tamoxifen is associated with endometrial pathology, the ATAC endometrial subprotocol was initiated to establish the background prevalence of pathology, and to assess prospectively the incidence and nature of intrauterine changes before and following endocrine therapy.

A multicentre study comparing cervicography and cytology in the detection of cervical intraepithelial neoplasia

Objective To evaluate in a multicentre setting the performance of cervicography compared with

Reasons for non-entry of patients with DCIS of the breast into a randomised trial (EORTC 10853)

In EORTC trial 10853, patients with histologically confirmed surgical clearance of ductal carcinoma in situ (DCIS) are being randomised to observation alone or to receive external radiation to the breast (50 Gy). So far, 190 patients have been entered from 27 centres. An analysis has been conducted of patients with DCIS presenting to 6 of the participating hospitals. Within these centres there was a total of 216 patients with biopsy confirmed DCIS, without invasion, between 1985 and 1989. However only 77 (36%) were entered into the trial. The major reason for non-entry was that DCIS was too extensive (76/139, 55%), so that in situ disease extended to the margins of excision. Other reasons for exclusion included prior breast cancer (18%), delay in histological diagnosis (6%) and a lump measuring more than 3 cm in diameter (4%). Only 6 patients (4%) refused to take part in the trial. Thus the eventual results of the trial may be applicable only to a minority of patients with DCIS.

Genomic Grade Index (GGI): feasibility in routine practice and impact on treatment decisions in early breast cancer.

Purpose Genomic Grade Index (GGI) is a 97-gene signature that improves histologic grade (HG) classification in invasive breast carcinoma. In this prospective study we sought to evaluate the feasibility of performing GGI in routine clinical practice and its impact on treatment recommendations. Methods Patients with pT1pT2 or operable pT3, N0-3 invasive breast carcinoma were recruited from 8 centers in Belgium. Fresh surgical samples were sent at room temperature in the MapQuant Dx™ PathKit for centralized genomic analysis. Genomic profiles were determined using Affymetrix U133 Plus 2.0 and GGI calculated using the MapQuant Dx® protocol, which defines tumors as low or high Genomic Grade (GG-1 and GG-3 respectively). Results 180 pts were recruited and 155 were eligible. The MapQuant test was performed in 142 cases and GGI was obtained in 78% of cases (n=111). Reasons for failures were 15 samples with <30% of invasive tumor cells (11%), 15 with insufficient RNA quality (10%), and 1 failed hybridization (<1%). For tumors with an available representative sample (≥ 30% inv. tumor cells) (n=127), the success rate was 87.5%. GGI reclassified 69% of the 54 HG2 tumors as GG-1 (54%) or GG-3 (46%). Changes in treatment recommendations occurred mainly in the subset of HG2 tumors reclassified into GG-3, with increased use of chemotherapy in this subset. Conclusion The use of GGI is feasible in routine clinical practice and impacts treatment decisions in early-stage breast cancer. Trial Registration ClinicalTrials.gov NCT01916837, http://clinicaltrials.gov/ct2/show/NCT01916837