S Pintens

Qualitative Assessment of the Progesterone Receptor and HER2 Improves the Nottingham Prognostic Index Up to 5 Years After Breast Cancer Diagnosis

PURPOSE To investigate whether the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) can improve the Nottingham Prognostic Index (NPI) in the classification of patients with primary operable breast cancer for disease-free survival (DFS). PATIENTS AND METHODS The analysis is based on 1,927 patients with breast cancer treated between 2000 and 2005 at the University Hospitals, Leuven. We compared performances of NPI with and without ER, PR and/or HER2. Validation was done on two external data sets containing 862 and 2,805 patients from Oslo (Norway) and Auckland (New Zealand), respectively. RESULTS In the Leuven cohort, median follow-up was 66 months, and 13.7% of patients experienced a breast cancer-related event. Positive staining for ER, PR, and HER2 was detected, respectively, in 86.9%, 75.5%, and 11.9% of patients. Based on multivariate Cox regression modeling, the improved NPI (iNPI) was derived as NPI - PR positivity + HER2 positivity. Validation results showed a risk group reclassification of 20% to 30% of patients when using iNPI with its optimal risk boundaries versus NPI, in a majority of patients to more appropriate risk groups. An additional 10% of patients were classified into the extreme risk groups, where clinical actions are less ambiguous. Survival curves of reclassified patients resembled more closely those for patients in the same iNPI group than those for patients in the same NPI group. CONCLUSION The addition of PR and HER2 to NPI increases its 5-year prognostic accuracy. The iNPI can be considered as a clinically useful tool for stratification of patients with breast cancer receiving standard of care.

Triple negative breast cancer: a study from the point of view of basal CK5/6 and HER-1

Aim: Basal-like breast tumours, as defined by microarrays, carry a poor prognosis and therapeutic options are limited to date. Often, these tumours are defined as oestrogen receptor (ER) negative/progesterone receptor (PR) negative/human epidermal growth factor receptor 2 (HER-2) negative (triple negative) by immunohistochemistry (IHC), but a more complete definition should include expression of basal cytokeratins (CK5/6, CK14 or CK17) and/or human epidermal growth factor receptor 1 (HER-1). The aim of this study was to investigate to what extent CK5/6 and HER-1 characterise the group of triple negative breast cancers. Methods: Expression of CK5/6 and HER-1 was studied by IHC in 25 triple negative breast carcinomas and 32 grade-matched, non-triple-negative controls. All 57 cases were further subjected to fluorescence in situ hybridisation to investigate HER-1 gene copy number. Results: CK5/6 and HER-1 expression was most frequent in triple negative tumours: 22 out of 25 cases (88.0%) expressed at least one of these markers (60.0% CK5/6 positive and 52.0% HER-1 positive). In the control group, CK5/6 and HER-1 expression was found in ER-negative but not in ER-positive tumours (ER negative/PR negative/HER-2 positive tumours: 20.0% CK5/6 positive and 46.7% HER-1 positive). HER-1 gene amplification was found in five cases only: four triple negative (16.0%) and one ER-negative control (ER negative/PR negative/HER-2 positive, 6.7%). Of interest, all five HER-1 amplified cases showed a remarkably homogeneous HER-1 expression pattern. Conclusion: Expression of CK5/6 and HER-1 is frequent in ER-negative breast cancers, in triple negative and in non-triple negative tumours. In a minority of cases, HER-1 overexpression may be caused by HER-1 gene amplification. Further studies are needed to investigate whether such cases might benefit from anti-HER-1 therapy

Short-Term Prognostic Index for Breast Cancer: NPI or Lpi

Axillary lymph node involvement is an important prognostic factor for breast cancer survival but is confounded by the number of nodes examined. We compare the performance of the log odds prognostic index (Lpi), using a ratio of the positive versus negative lymph nodes, with the Nottingham Prognostic Index (NPI) for short-term breast cancer specific disease free survival. A total of 1818 operable breast cancer patients treated in the University Hospital of Leuven between 2000 and 2005 were included. The performance of the NPI and Lpi were compared on two levels: calibration and discrimination. The latter was evaluated using the concordance index (cindex), the number of patients in the extreme groups, and difference in event rates between these. The NPI had a significant higher cindex, but a significant lower percentage of patients in the extreme risk groups. After updating both indices, no significant differences between NPI and Lpi were noted.

Biology and prognosis by age of primary operable breast cancer.

Abstract #2082 Introduction Breast cancer (BC) biology and prognosis are age dependent. We studied the effect of age on BC biology, treatment and prognosis.
 Methods Data from 2059 consecutive patients, primary operated for invasive BC in UZ Leuven (01/01/00–01/06/05), were used. Patients with ≥ 3.5 yrs follow-up were included (n=1064) to study relapse in relation to age (logistic regression).
 Results Early relapse in BC is age-related, decreasing 3.2% each yr for patients 60 yrs: early relapse increases 5.5% each yr (p=0.0007, 95% CI OR: 1.021-1.082). The positive lymph node status is decreasing 3.5% each yr 60 years. For the progesterone receptor (PR), this depends quadratically on the age at diagnosis (p=0.0108, 95% CI OR=0.999-1.000), decreasing Conclusion Early relapse was higher with increasing/decreasing age, starting from age 60. This goes in parallel with the U-shape curve of lymph node involvement (Fig1). Increased relapse and lymph node positivity in elderly might partially be a reflection of the fact that BC is diagnosed in a later stage in elderly patients but might also be related to different biological behavior or to decreased use of adjuvant systemic treatment. HER-2 overexpression decreases with age and age related differences in ER and PR expression as well as tumor grading are observed (Fig 2).
 Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2082.