Screen-detected breast cancers have a lower mitotic activity index

We know that screening for breast cancer leads to detection of smaller tumours with less lymph node metastases. Could it be possible that the decrease in mortality after screening is not only caused by this earlier stage, but also by a different mitotic activity index (MAI) of the tumours that are detected by screening? Is MAI a prognostic factor for recurrence-free survival? A retrospective study was carried out of 387 patients with breast cancer, treated at the University Hospital Nijmegen between January 1992 and September 1997. Ninety patients had screen-detected breast cancer, 297 patients had breast cancers detected outside the screening programme. The MAI, other prognostic factors and recurrence-free survival were determined. In non-screen-detected tumours the MAI is twice as high as in screen-detected tumours, even after correction for age took place. The MAI correlated well with other tumour characteristics. The MAI in itself is a prognostic factor for recurrence-free survival. Favourable outcome in screen detected breast cancer is not entirely caused by detecting cancer in early stages: quantitative features such as the MAI indicate a less malignant character of screen detected breast cancer. The MAI is an independent prognostic factor for recurrence-free survival. © 2000 Cancer Research Campaig

Number of apoptotic cells as a prognostic marker in invasive breast cancer

Apoptosis plays an important role in tumorigenesis. Tumour growth is determined by the rate of cell proliferation and cell death. We counted the number of apoptotic cells in haematoxylin and eosin (H&E)-stained tumour sections in series of 172 grade I and II invasive breast cancers with long-term follow-up. The number of apoptotic cells in ten high-power fields were converted to the number of apoptotic cells per mm2to obtain the apoptotic index (AI). The AI showed a positive correlation to the mitotic activity index (MAI) (P = 0.0001), histological grade (P< 0.0001) and worse tumour differentiation. Patients with high AI showed shorter overall survival than patients with low AI in the total group as well as in the lymph node-positive group. Tumour size, MAI, lymph node status and AI were independent prognostic indicators in multivariate analysis. The AI was shown to be of additional prognostic value to the MAI in the total patients group as well as in the lymph node-positive group. The correlation between the AI and the MAI points to linked mechanisms of apoptosis and proliferation. Since apoptotic cells can be counted with good reproducibility in H&E-stained tumour sections, the AI may be used as an additional prognostic indicator in invasive breast cancer. © 2000 Cancer Research Campaig

Screen-detected vs clinical breast cancer: the advantage in the relative risk of lymph node metastases decreases with increasing tumour size

Screen-detected (SD) breast cancers are smaller and biologically more indolent than clinically presenting cancers. An often debated question is: if left undiagnosed during their preclinical phase, would they become more aggressive or would they only increase in size? This study considered a registry-based series (1988–1999) of 3329 unifocal, pT1a-pT3 breast cancer cases aged 50–70 years, of which 994 were SD cases and 2335 clinical cases. The rationale was that (1) the average risk of lymph node involvement (N+) is lower for SD cases, (2) nodal status is the product of biological aggressiveness and chronological age of the disease, (3) for any breast cancer, tumour size is an indicator of chronological age, and (4) for SD cases, tumour size is specifically an indicator of the duration of the preclinical phase, that is, an inverse indicator of lead time. The hypothesis was that the relative protection of SD cases from the risk of N+ and, thus, their relative biological indolence decrease with increasing tumour size. The odds ratio (OR) estimate of the risk of N+ was obtained from a multiple logistic regression model that included terms for detection modality, tumour size category, patient age, histological type, and number of lymph nodes recovered. A term for the detection modality-by-tumour size category interaction was entered, and the OR for the main effect of detection by screening vs clinical diagnosis was calculated. This increased linearly from 0.05 (95% confidence interval: 0.01–0.39) in the 2–7 mm size category to 0.95 (0.64–1.40) in the 18–22 mm category. This trend is compatible with the view that biological aggressiveness of breast cancer increases during the preclinical phase

Detection methods predict differences in biology and survival in breast cancer patients

BackgroundThe aim of this study was to measure the biological characteristics involved in tumorigenesis and the progression of breast cancer in symptomatic and screen-detected carcinomas to identify possible differences.MethodsFor this purpose, we evaluated clinical-pathological parameters and proliferative and apoptotic activities in a series of 130 symptomatic and 161 screen-detected tumors.ResultsAfter adjustment for the smaller size of the screen-detected carcinomas compared with symptomatic cancers, those detected in the screening program presented longer disease-free survival (RR = 0.43, CI = 0.19-0.96) and had high estrogen and progesterone receptor concentrations more often than did symptomatic cancers (OR = 3.38, CI = 1.72-6.63 and OR = 3.44, CI = 1.94-6.10, respectively). Furthermore, the expression of bcl-2, a marker of good prognosis in breast cancer, was higher and HER2/neu expression was lower in screen-detected cancers than in symptomatic cancers (OR = 1.77, CI = 1.01-3.23 and OR = 0.64, CI = 0.40-0.98, respectively). However, when comparing prevalent vs incident screen-detected carcinomas, prevalent tumors were larger (OR = 2.84, CI = 1.05-7.69), were less likely to be HER2/neu positive (OR = 0.22, CI = 0.08-0.61) and presented lower Ki67 expression (OR = 0.36, CI = 0.17-0.77). In addition, incident tumors presented a shorter survival time than did prevalent ones (RR = 4.88, CI = 1.12-21.19).ConclusionsIncident carcinomas include a variety of screen-detected carcinomas that exhibit differences in biology and prognosis relative to prevalent carcinomas. The detection method is important and should be taken into account when making therapy decisions

Evaluation of human-papillomavirus testing and visual inspection for cervical cancer screening in Rwanda

Background A pilot screening campaign in Rwanda, based on careHPV-testing followed by visual inspection with acetic acid triage (careHPV+VIA triage), was evaluated against other WHO-recommended screening options, namely HPV screen-and-treat and VIA screen-and-treat. Methods 764 women aged 30-69 underwent at visit 1: i) VIA, and cervical cell collection for ii) careHPV in Rwanda, and iii) liquid-based cytology and GP5+/6+ HR-HPV PCR in The Netherlands. All 177 women positive by VIA, careHPV and/or PCR were recalled, of whom 84% attended. At visit 2, VIA was again used to triage screen-positive women for treatment and to obtain biopsies from all women either from visible lesions or at 12 o’clock of the squamocolumnar junction. Cross-sectional screening indices were estimated primarily against histological high-grade squamous intraepithelial lesions or worse (hHSIL+), after imputation of missing histology data, based on 1-visit or 2-visit approaches. Results In a 1-visit screen-and-treat approach, VIA had sensitivity and specificity of 41% and 96%, respectively, versus 71% and 88% for careHPV, and 88% and 86% for PCR. In a 2-visit approach (in which hHSIL+ imputed among women without visit 2 were considered untreated) careHPV sensitivity dropped to 59% due to loss of 13% of hHSIL+. For careHPV+VIA triage, sensitivity dropped further to 35%, as another 24% of hHSIL+ were triaged to no treatment. Conclusions CareHPV was not as sensitive as gold-standard PCR, but detected considerably more hHSIL+ than VIA. However, due to careHPV-positive hHSIL+ women being lost to follow-up and/or triaged to no treatment, 2-visit careHPV+VIA triage did not perform better than VIA screen-and-treat