Anti-apoptotic phenotype is associated with decreased locoregional recurrence rate in breast cancer.
OBJECTIVE
Tumor stage and nodal status are the most important factors predicting locoregional recurrence in breast cancer. We wanted to investigate the prognostic value of some newer molecular genetic markers for the occurrence of a locoregional recurrence, in order to improve the selection of patients for locoregional adjuvant therapy.


METHODS
Bcl-2, p53, MIB-1, pS2 and CD44v6 were determined immunohistochemically on formalin-fixed and paraffin embedded tumour tissues of 163 patients treated by modified radical mastectomy between 1982 and 1987. Postoperative irradiation was given to 35 patients to the intermammary chain only and to only 13 (8%) patients to the chest wall with or without the regional lymph nodes. Node-positive patients were treated with CAF adjuvant chemotherapy and were randomized for whether or no additional Medroxyprogesteroneacetate (MPA). A multivariate analysis was performed on a number of potential prognostic factors. The risk for locoregional recurrence was estimated using the competing risk approach.


RESULTS
After a median period of 7.5 years 28 patients developed a locoregional recurrence. The cumulative incidence of loco-regional recurrence at 10 years was 17%. Bcl-2 and p53 were found to be independent factors predicting locoregional recurrence, whereas a trend was found for MIB-1. Increased Bcl-2 as well as p53 expression were associated with a decreased risk, whereas the increased presence of MIB-1 was associated with an increased risk.


CONCLUSIONS
Results indicate that molecular markers of apoptosis as well as proliferation provide additional information for the risk of locoregional recurrence after modified radical mastectomy. If confirmed, these markers may play a role in the selection of appropriate locoregional adjuvant treatment after primary surgery.
Jager
J J
JJ
Radiotherapeutisch Instituut Limburg, Heerlen, Maastricht, The Netherlands.
Jansen
R L
RL
Arends
J W
JW
Joosten-Achjanie
S
S
Volovics
L
L
Schouten
L J
LJ
De Jong
J M
JM
Meyenfeldt
M F
MF
Blijham
G H
GH
D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005819:Genetic Markers; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D019394:Ki-67 Antigen; D015411:Mastectomy, Modified Radical; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis; D010641:Phenotype; D011003:Ploidies; D011506:Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016196:S Phase; D000071163:Trefoil Factor-1; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D025521:Tumor Suppressor Proteins
D034961:Antigens, Nuclear; C112697:CD44v6 antigen; D005819:Genetic Markers; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D017258:Medroxyprogesterone Acetate