Predicting aggressive outcome in T1N0M0 breast cancer

Abstract

Despite the excellent overall prognosis, unpredictable breast cancer recurrences and deaths also occur among T1N0M0 patients. We have evaluated clinically applicable methods for identifying aggressive outcome in T1N0M0 breast cancer. The material is based on aggressive T1N0M0 invasive ductal and lobular carcinomas diagnosed in Turku University Hospital and Jyväskylä Central Hospital, Finland, during 1987 -1997. We studied all the T1N0M0 breast cancers that had led to recurrency or death (n ¼ 21, 95% T1cN0M0) during the follow-up period (4 -14 years). The study is based on statistical analyses of matched case -control data in which the prognostic factors of each individual patient with aggressive disease were compared with control patients (n ¼ 45) individually matched by tumour size, age at diagnosis, histological type of tumour and length of follow-up. The cancer cases were examined for clinically applicable conventional and immunohistochemical pathologic prognostic factors. High Ki-67 immunopositivity was the strongest prognosticator of breast cancer death or recurrence in T1N0M0 breast cancer. Also, high p53 immunopositivity, low oestrogen receptor immunopositivity and Her-2/neu oncogene amplification by chromogen in situ hybridisation were reliable indicators of unfavourable outcome. Our statistical methods also allowed us to determine for the present material a range of clinical significance for each immunohistochemical prognostic feature with the associated relative risk for breast cancer death and recurrence. The paper suggests guidelines for predicting aggressive outcome in T1N0M0 breast cancer.

Biological profile of oestrogen receptor positive primary breast cancers in the elderly and response to primary endocrine therapy

“…Nevertheless, other markers such as PgR, ER␤2, Human Epidermal Growth Factor Receptor 2 (HER2), Epidermal Growth Factor Receptor (EGFR) and Ki-67 (a marker of proliferation) have also been shown to have prognostic and predictive relevance [14][15][16][17][18][19][20]. Defining the pattern of expression of these markers in ER␣+ breast cancer in elderly women and their predictive power relating to response to treatment could contribute significantly to the selection of an optimum therapeutic agent.…”

Proliferation marker securin identifies favourable outcome in invasive ductal breast cancer

“…Securin and Ki-67 immunopositivities were determined by the fraction (%) of positively stained tumour cells and securin also by the intensity of staining (0, no staining; 1, weakly stained; 2, moderately stained; 3, strongly stained) at the areas of most pronounced staining, usually at the most cellular, infiltrating border of the tumour. Analysis of Ki-67 positivity was based on cutoff points at 10 and 20% of cancer cells (Ki-67o10%, 10%pKi-67p20% and Ki-67420%) adopted from clinical practice and based on research on breast cancer samples from Finland and other countries (Kronqvist et al, 2004;de Azambuja et al, 2007;Railo et al, 2007). The same cutoff points were applied for securin immunohistochemistry.…”

Association between tumour characteristics and HER-2/neu by immunohistochemistry in 1362 women with primary operable breast cancer

“…2 This has been confirmed in the clinic: women with HER-2/neu positive breast cancer have a worse prognosis than those with HER-2/neu negative cancers; this is also true for T1N0M0 tumours. [3][4][5][6] Furthermore, HER-2/neu overexpression has been correlated with poor prognostic tumour characteristics such as higher histological grade, S phase fraction, increased tumour size, number of involved lymph nodes, lymphoid infiltration, p53 mutation, absence of bcl-2, absence of lobular histology, and negative or lower oestrogen receptor (ER) expression. [7][8][9][10][11][12][13][14][15] As a consequence, several, but not all, studies have confirmed that HER-2/neu overexpressing tumours show a lower response to tamoxifen in metastatic or early breast cancer.…”