Breast cancer. Quality Assurance and Prognosis

University dissertation from Department of Surgery, Clinical Sciences Lund, Lund University

Abstract: Abstract

Background. The Swedish national cancer strategy programme published in 2009 emphasises the patient perspective and focuses on the patient process. Over the years the different modalities in breast cancer treatment are changing position, making accurate diagnosis and quality assurance in breast pathology even more important than before.

Aims. The aim of paper I was to examine overall survival in women with micrometastases in relation to node-negative women. In paper II four different routine methods for the pathological work-up of frozen section negative sentinel nodes (SN) were compared to find the method showing the largest fraction of patients with small deposits in SNs, in order to achieve the highest possible confidence in the negative status. In paper III the aim was to determine whether screening status influences the proportion of patients with additional positive nodes in the axillary lymph node dissection (ALND) specimen after the SNs have been diagnosed with micrometastases. Paper IV deals with immunohistochemistry with the aim of comparing the prevalence of oestrogen receptor (ER)-positive patients when the ER status was determined by three different antibodies and heat-induced epitope retrieval (HIER) methods in premenopausal stage II patients.

Material. In paper I the study cohort consisted of 6,959 women with T1-T3, N0-N1, M0 primary breast cancer aged below 75 years and registered in the Danish Breast Cancer Database from 1 January 1990 to 31 October 1994. The study cohort in paper II was a consecutive series of 1,576 women with a first primary operable breast cancer treated at the University Hospital of Lund from 1 January 2001 to 31 December 2009, of whom 1,098 had sentinel node biopsy (SNB). In paper III the study cohort was 1,993 consecutive women with first primary unilateral breast cancer, of whom 1,458 had SNB, treated at Skåne University Hospital, Lund between 2001 and 2011. In paper IV ER status was assessed on tissue microarrays, with three different ER antibodies and HIER methods: 1D5 in citrate pH 6, SP1 in Tris pH 9 (n=390) and PharmDx in citrate pH 6 (n=361).
Results. Paper I showed in a multivariate analysis that women with micrometastases had a significantly higher risk of death than did node-negative women (adjusted relative risk = 1.49, 95% CI: 1.18–1.90) (p<0.01). The result of paper II was that a combination of teamwork and the addition of intensive IHC for cytokeratin (CK) at fixed levels resulted in 13% more patients with isolated tumour cells and micrometastases than if a method with step sections at fixed intervals were used. In paper III the results of a logistic regression analysis showed 5 times higher odds for further metastases in the ALND in patients with micrometastases in SNs when symptomatic presentation was compared with screen-detected breast cancer. The findings in paper IV were that the prevalence of ER-positivity was higher with SP1 (75% and 72%) compared with 1D5 (68% and 66%) and PharmDx (66% and 62%) at cut-offs of 1% and 10%, respectively. The repeatability was good for all antibodies and cut-offs with overall agreement ≥93%.

Conclusion. Patients with micrometastases detected in ALND have an inferior 10-year overall survival compared with node-negative patients. SN examination with step sections at fixed levels including CK at each level is important in ensuring that the node-negative group really is node-negative. Screen-detected breast cancer patients with micrometastases have 5-time lesser odds for additional metastases in the completion ALND compared with symptomatic patients, and are thereby candidates for the omission of completion ALND. The prevalence of ER-positive breast cancer patients is dependent on the antibody and HIER method.