Clinical studies of apoptosis and proliferation in breast cancer.
The interaction between cell death and cell proliferation determines the growth dynamics of all tissues. Studies are described here which relate the changes in proliferation and apoptosis that occur in human breast cancer during medical therapeutic manoeuvres. Xenograft studies strongly support the involvement of increased apoptosis as well as decreased proliferation after oestrogen withdrawal, and limited studies in clinical samples confirm the involvement of both processes. Cytotoxic chemotherapy induces increases in apoptosis within 24 h of starting treatment. However, after 3 months therapy the residual cell population shows apoptotic and proliferation indices much below pretreatment levels. Further molecular studies of this "dormant" population are important to characterise the mechanism of their resistance to drug therapy. The early changes in proliferation and apoptosis may provide useful intermediate response indices.
Dowsett
M
M
Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.
Archer
C
C
Assersohn
L
L
Gregory
R K
RK
Ellis
P A
PA
Salter
J
J
Chang
J
J
Mainwaring
P
P
Boeddinghaus
I
I
Johnston
S R
SR
Powles
T J
TJ
Smith
I E
IE
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D004967:Estrogens; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology; D011247:Pregnancy; D013629:Tamoxifen / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D019394:Ki-67 Antigen; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol