Changes in microvessel density as assessed by CD34 antibodies after primary chemotherapy in human breast cancer.
BACKGROUND
Several papers have shown that quantitationof tumor angiogenesis in primary breast cancer by counting blood vessels gives an independent assessment of prognosis. The impact of chemotherapy +/- endocrine therapy on the extent of angiogenesis is unknown.


METHODS
Matched pair histological tumor samples were obtained before and after primary chemotherapy from 120 breast cancer patients recruited in the same institution. The first 55 cases received cyclophosphamide, methotrexate, and 5-fluorouracil +/- Tamoxifen, whereas the subsequent 65 were submitted to single agent epirubicin. Patients underwent an incisional biopsy at diagnosis and definitive surgery on completion of three or four chemotherapy cycles. Microvessel density (MVD) was performed after staining with the CD34 monoclonal antibody.


RESULTS
MVD slightly decreased after chemotherapy [median 51.26 mm(2) (range 2.33-163.1) and 44.27 mm(2) (2.33-121.16; P < 0.001)]; this small reduction neither correlated with tumor response nor with changes in Ki67 expression. MVD at baseline significantly correlated with MVD assessed at definitive surgery (Spearman r = 0.70, P < 0.001). In multivariate analysis, c-erbB2 status showed an independent role in predicting the reduction in MVD that just failed to attain the statistical significance (P = 0.08), whereas baseline parameters, such as T, N, steroid hormone receptor, bcl-2, p53, c-erbB2, and Ki67 expression, did not enter the model.


CONCLUSIONS
Primary chemotherapy is able to modestly reduce the MVD in breast tumors. This small change is not biologically important, because the baseline neoangiogenesis status is not substantially changed. The change in microvessel count after chemotherapy could be potentially influenced by the c-erbB2 status.
Bottini
Alberto
A
Breast Cancer Unit, Azienda Ospedaliera Istituti Ospitalieri, Cremona, Italy.
Berruti
Alfredo
A
Bersiga
Alessandra
A
Brizzi
Maria Pia
MP
Allevi
Giovanni
G
Bolsi
Giovanna
G
Aguggini
Sergio
S
Brunelli
Antonio
A
Betri
Enrico
E
Generali
Daniele
D
Scaratti
Lorena
L
Bertoli
Giovanni
G
Alquati
Palmiro
P
Dogliotti
Luigi
L
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D018952:Antigens, CD34 / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008727:Methotrexate / Q000008:administration & dosage; D008833:Microcirculation; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D003520:Cyclophosphamide; D015251:Epirubicin; D005472:Fluorouracil; D019394:Ki-67 Antigen; D008727:Methotrexate; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D016159:Tumor Suppressor Protein p53