title: Expression of Bcl-2 in node-negative breast cancer is associated with various prognostic factors, but does not predict response to one course of perioperative chemotherapy.
abstract: The aim of this study was to assess relationships between Bcl-2 expression, response to chemotherapy and a number of pathological and biological tumour parameters in premenopausal, lymph node-negative breast cancer patients. Expression of Bcl-2 was determined using immunohistochemistry on paraffin-embedded sections in a series of 441 premenopausal, lymph node-negative breast cancers of patients randomised to receive perioperative chemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide) or no perioperative chemotherapy. Immunohistochemistry of Bcl-2 was evaluated by scoring both staining intensity (0-3) and number of positive cells (0-2). Using these scores tumours were grouped into categories 0-6. It was found that 9.2% of the tumours were completely negative (0), 17.2% weakly (1 + 2), 41.6% moderately (3 + 4) and 31.9% strongly positive (5 + 6) for Bcl-2. A positive correlation was found between high Bcl-2 expression and oestrogen (P < 0.001) and progesterone receptor positivity (P < 0.001) and low tumour grade (P < 0.001), whereas high Bcl-2 expression was negatively correlated with p53 (P < 0.001) and c-erb-B-2 positively (P < 0.001), high Ki-67 index (P < 0.001), mitotic index (P < 0.001) and large tumour size (P = 0.006). Patients with tumours expressing high levels of Bcl-2 (overall score 3-6) had a significantly better disease-free (P = 0.004) and overall (P = 0.009) survival. However, in a multivariate model this association no longer remained significant. There was a trend for an effect of adjuvant chemotherapy on disease-free survival both for patients with Bcl-2-positive (HR-0.61, 95% CI 0.35-1.06, P = 0.07) and negative (HR = 0.55, 95% CI 0.27-1.12, P = 0.09) breast tumours at a median follow-up of 49 months. The level of Bcl-2 expression does not seem to predict response to perioperative chemotherapy in premenopausal, lymph node-negative breast cancer patients. High levels of Bcl-2 are preferentially expressed in well-differentiated tumours and are associated with favourable prognosis. However, Bcl-2 expression is not an independent prognostic factor in this patient series.
authors.affiliation: Department of Surgery, Leiden University Hospital, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: van Slooten
authors.forename: P C
authors.initials: PC
authors.lastname: Clahsen
authors.forename: J H
authors.initials: JH
authors.lastname: van Dierendonck
authors.forename: C
authors.initials: C
authors.lastname: Duval
authors.forename: C
authors.initials: C
authors.lastname: Pallud
authors.forename: A M
authors.initials: AM
authors.lastname: Mandard
authors.forename: A
authors.initials: A
authors.lastname: Delobelle-Deroide
authors.forename: C J
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: M J
authors.initials: MJ
authors.lastname: van de Vijver
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001940:Breast / Q000737:chemistry / Q000473:pathology; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000601:surgery; D002278:Carcinoma in Situ / Q000737:chemistry; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008679:Metaplasia; D009361:Neoplasm Invasiveness; D011182:Postoperative Care; D011237:Predictive Value of Tests; D017697:Premenopause; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2; D012016:Reference Values
chemical_list: D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil